Science.gov

Sample records for meningitis cerebrospinal fluid

  1. Utility of cerebrospinal fluid cortisol level in acute bacterial meningitis

    PubMed Central

    Mehta, Anish; Mahale, Rohan R.; Sudhir, Uchil; Javali, Mahendra; Srinivasa, Rangasetty

    2015-01-01

    Background: Meningitis remains a serious clinical problem in developing as well as developed countries. Delay in diagnosis and treatment results in significant morbidity and mortality. The role and levels of intrathecal endogenous cortisol is not known. Objective: To study the cerebrospinal fluid (CSF) cortisol levels and to evaluate its role as a diagnostic and therapeutic marker in acute bacterial meningitis. Materials and Methods: Thirty patients with acute bacterial meningitis with no prior treatment were evaluated. Cortisol levels were compared with 20 patients with aseptic (viral) meningitis and 25 control subjects. Results: Mean CSF cortisol level was 13.85, 3.47, and 1.05 in bacterial meningitis, aseptic meningitis, and controls, respectively. Mean CSF cortisol level in bacterial meningitis was significantly higher as compared to controls (P < 0.001). There was significant difference in CSFcortisol levels in bacterial and aseptic meningitis (P < 0.001). Conclusions: Cortisol levels in CSF are highly elevated in patients with acute bacterial meningitis. This suggests that intrathecalcortisol may serve as a valuable, rapid, relatively inexpensive diagnostic marker in discriminatingbetween bacterial and aseptic meningitis. This helps in earlier institution of appropriate treatment and thereby decreasing morbidity and mortality. PMID:26019421

  2. Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography

    SciTech Connect

    Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.

    1982-11-01

    Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

  3. Detection of High Cerebrospinal Fluid Levels of (1?3)-?-d-Glucan in Cryptococcal Meningitis

    PubMed Central

    Rhein, Joshua; Bahr, Nathan C.; Morawski, Bozena M.; Schutz, Charlotte; Zhang, Yonglong; Finkelman, Malcolm; Meya, David B.; Meintjes, Graeme; Boulware, David R.

    2014-01-01

    Background ?(1?3)-?-d-Glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections. However, BDG is not thought to be useful in diagnosing cryptococcosis. We evaluated the utility of BDG as an adjunct diagnostic tool for patients infected with human immunodeficiency virus (HIV) and presenting with suspected cryptococcal meningitis. Methods ?The Fungitell assay was used to measure BDG concentrations in cerebrospinal fluid (CSF) (n = 177) and serum (n = 109) of HIV-infected Ugandans and South Africans with suspected meningitis. Correlations between BDG concentrations and quantitative CSF cryptococcal cultures, CSF cryptococcal antigen (CRAG) titers, and 18 different CSF cytokine concentrations were assessed using non-parametric tests. Mixed models evaluated longitudinal changes in CSF BDG concentrations. Survival analyses were used to evaluate BDG's relationship with mortality. Results ?The Fungitell BDG assay provided 89% sensitivity and 85% specificity in CSF for cryptococcal meningitis. Serum sensitivity was suboptimal (79%). Cerebrospinal fluid BDG concentrations at diagnosis were median (interquartile range) 343 (200–597) pg/mL in cryptococcal patients and 37 (23–46) pg/mL in patients without cryptococcosis. Sensitivity in CSF improved to 98% (53 of 54) when initial fungal burdens were ?10 000 colony-forming units/mL. (1?3)-?-d-Glucan normalized rapidly after initiating antifungal therapy. Baseline BDG concentrations correlated with CSF fungal burden (rho = 0.820; P < .001), CSF CRAG lateral flow assay titers (rho = 0.780, P < .001), and monocyte chemotactic protein-1 levels in CSF (P = .047). In patients with cryptococcal meningitis, BDG ?500 pg/mL at diagnosis was associated with increased 10-week mortality. Conclusions ?(1?3)-?-d-Glucan is detectable in the CSF of HIV-infected patients with Cryptococcus, and it may provide useful prognostic information. Sensitivity is less than CRAG; however, BDG normalizes rapidly, unlike CRAG, making BDG potentially useful in diagnosing recurrent episodes. PMID:25734173

  4. Clinical Prognosis in Neonatal Bacterial Meningitis: The Role of Cerebrospinal Fluid Protein

    PubMed Central

    Zhao, Dongying; Ren, Fang; Luo, Zhongcheng; Zhang, Yongjun

    2015-01-01

    Neonates are at high risk of meningitis and of resulting neurologic complications. Early recognition of neonates at risk of poor prognosis would be helpful in providing timely management. From January 2008 to June 2014, we enrolled 232 term neonates with bacterial meningitis admitted to 3 neonatology departments in Shanghai, China. The clinical status on the day of discharge from these hospitals or at a postnatal age of 2.5 to 3 months was evaluated using the Glasgow Outcome Scale (GOS). Patients were classified into two outcome groups: good (167 cases, 72.0%, GOS = 5) or poor (65 cases, 28.0%, GOS = 1–4). Neonates with good outcome had less frequent apnea, drowsiness, poor feeding, bulging fontanelle, irritability and more severe jaundice compared to neonates with poor outcome. The good outcome group also had less pneumonia than the poor outcome group. Besides, there were statistically significant differences in hemoglobin, mean platelet volume, platelet distribution width, C-reaction protein, procalcitonin, cerebrospinal fluid (CSF) glucose and CSF protein. Multivariate logistic regression analyses suggested that poor feeding, pneumonia and CSF protein were the predictors of poor outcome. CSF protein content was significantly higher in patients with poor outcome. The best cut-offs for predicting poor outcome were 1,880 mg/L in CSF protein concentration (sensitivity 70.8%, specificity 86.2%). After 2 weeks of treatment, CSF protein remained higher in the poor outcome group. High CSF protein concentration may prognosticate poor outcome in neonates with bacterial meningitis. PMID:26509880

  5. Cerebrospinal Fluid Culture Positivity and Clinical Outcomes After Amphotericin-Based Induction Therapy for Cryptococcal Meningitis

    PubMed Central

    Rolfes, Melissa A.; Rhein, Joshua; Schutz, Charlotte; Taseera, Kabanda; Nabeta, Henry W.; Huppler Hullsiek, Kathy; Akampuira, Andrew; Rajasingham, Radha; Musubire, Abdu; Williams, Darlisha A.; Thienemann, Friedrich; Bohjanen, Paul R.; Muzoora, Conrad; Meintjes, Graeme; Meya, David B.; Boulware, David R.

    2015-01-01

    Background.?Amphotericin-based combination antifungal therapy reduces mortality from human immunodeficiency virus (HIV)-associated cryptococcal meningitis. However, 40%–50% of individuals have positive cerebrospinal fluid (CSF) fungal cultures at completion of 2 weeks of amphotericin induction therapy. Residual CSF culture positivity has historically been associated with poor clinical outcomes. We investigated whether persistent CSF fungemia was associated with detrimental clinical outcomes in a contemporary African cohort. Methods.?Human immunodeficiency virus-infected individuals with cryptococcal meningitis in Uganda and South Africa received amphotericin (0.7–1.0 mg/kg per day) plus fluconazole (800 mg/day) for 2 weeks, followed by “enhanced consolidation” therapy with fluconazole 800 mg/day for at least 3 weeks or until cultures were sterile, and then 400 mg/day for 8 weeks. Participants were randomized to receive antiretroviral therapy (ART) either 1–2 or 5 weeks after diagnosis and observed for 6 months. Survivors were classified as having sterile or nonsterile CSF based on 2-week CSF cultures. Mortality, immune reconstitution inflammatory syndrome (IRIS), and culture-positive relapse were compared in those with sterile or nonsterile CSF using Cox regression. Results.?Of 132 participants surviving 2 weeks, 57% had sterile CSF at 2 weeks, 23 died within 5 weeks, and 40 died within 6 months. Culture positivity was not significantly associated with mortality (adjusted 6-month hazard ratio, 1.2; 95% confidence interval, 0.6–2.3; P = .28). Incidence of IRIS or relapse was also not significantly related to culture positivity. Conclusions.?Among patients, all treated with enhanced consolidation antifungal therapy and ART, residual cryptococcal culture positivity was not found to be associated with poor clinical outcomes. PMID:26716103

  6. (1,3)-?-d-glucan in cerebrospinal fluid for diagnosis of fungal meningitis associated with contaminated methylprednisolone injections.

    PubMed

    Malani, Anurag N; Singal, Bonita; Wheat, L Joseph; Al Sous, Ola; Summons, Theresa A; Durkin, Michelle M; Pettit, April C

    2015-03-01

    Prompt diagnosis and treatment of fungal meningitis are critical, but culture is insensitive. (1,3)-?-d-Glucan (BDG) testing is FDA approved for serological diagnosis of invasive fungal disease; however, BDG testing is not approved for cerebrospinal fluid (CSF), and the appropriate cutoff value is unknown. We aimed to validate the diagnostic accuracy of CSF BDG measurements for fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). A retrospective observational study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November 2013 to February 2014. Patients were included if they had received a contaminated MPA injection. Cases were classified as probable or proven meningitis according to Centers for Disease Control and Prevention guidelines. CSF BDG testing was performed according to the package insert instructions for serum samples, and results were validated using Clinical and Laboratory Standards Institute procedures (MiraVista Diagnostics). Of 233 patients, 45 had meningitis (28 proven cases), 53 had spinal/paraspinal infections (19 proven cases), and 135 did not develop disease. Using the manufacturer's cutoff value (?80 pg/ml), the sensitivity and specificity were 96% and 95%, respectively, for proven meningitis and 84% and 95% for probable or proven meningitis. Receiver operating characteristic analysis identified the optimal cutoff value for proven meningitis to be 66 pg/ml (sensitivity, 100%; specificity, 94%) and that for probable or proven meningitis to be 66 pg/ml (sensitivity, 91%; specificity, 92%). Our results suggest that CSF BDG measurements are highly sensitive and specific for the diagnosis of fungal meningitis associated with contaminated MPA injections. Further study on the utility of CSF BDG testing for other types of fungal meningitis is needed. PMID:25540391

  7. Diagnostic Value of T-Cell Interferon-? Release Assays on Cerebrospinal Fluid for Tuberculous Meningitis

    PubMed Central

    Zhang, Yueqiu; Shi, Xiaochun; Zhang, Yao; Liu, Xiaoqing

    2015-01-01

    Diagnosis of tuberculous meningitis (TBM) remains a challenge. This study aimed to evaluate the performance of T-SPOT.TB test on cerebrospinal fluid mononuclear cells (CSFMCs) for suspected TBM patients. 43 consecutive patients with suspected TBM were enrolled in the study from June 2011 to September 2014. T-SPOT.TB was performed on both CSFMCs and peripheral blood mononuclear cells (PBMCs). The final diagnosis of TBM was independent of the T-SPOT.TB result. The diagnostic sensitivity, specificity, predictive value, and likelihood ratio of T-SPOT.TB on CSFMCs and PBMCs were analyzed. Of the 43 patients, 12 (27.9%) were finally diagnosed with TBM, 28 (65.1%) with non-TBM, and 3 (7.0%) with indeterminate diagnoses. Of 40 cases with definite diagnoses, the sensitivity and specificity were 92.0% and 96.0% for T-SPOT.TB on CSFMCs, and 83.0% and 82.0% for T-SPOT.TB on PBMCs, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of T-SPOT.TB on CSFMCs were 85.0% and 96.0%, respectively. The PPV and NPV were 67.0% and 92.0% for T-SPOT.TB on PBMCs. The difference of T-SPOT.TB between CSFMCs and PBMCs was not significant so far as sensitivity, specificity, PPV, and NPV were concerned (P>0.05 for each). However, T-SPOT.TB on CSFMC and CSFMC: PBMC in TBM cases seemed higher than that in non-TBM cases. Our study further showed that T-SPOT.TB on CSFMCs might be a rapid and accurate diagnostic test for TBM. CSFMC: PBMC T-SPOT.TB ratio might be useful for the early diagnosis of TBM. PMID:26545256

  8. Real-time PCR for detection of Streptococcus suis serotype 2 in cerebrospinal fluid of human patients with meningitis.

    PubMed

    Nga, Tran Vu Thieu; Nghia, Ho Dang Trung; Tu, Le Thi Phuong; Diep, To Song; Mai, Nguyen Thi Hoang; Chau, Tran Thi Hong; Sinh, Dinh Xuan; Phu, Nguyen Hoan; Nga, Tran Thi Thu; Chau, Nguyen Van Vinh; Campbell, James; Hoa, Ngo Thi; Chinh, Nguyen Tran; Hien, Tran Tinh; Farrar, Jeremy; Schultsz, Constance

    2011-08-01

    Streptococcus suis serotype 2 is an emerging zoonotic pathogen and is the main cause of acute bacterial meningitis in adult patients in Vietnam. We developed an internally controlled real-time PCR for detection of S. suis serotype 2 in cerebrospinal fluid (CSF) samples targeted at the cps2J gene. Sensitivity and specificity in culture-confirmed clinical samples were 100%. The PCR detected S. suis serotype 2 infection in 101 of 238 (42.4%) prospectively collected CSF samples, of which 55 (23%) were culture positive. Culture-negative but PCR-positive CSF samples were significantly associated with the use of antimicrobial agents before admission. S. suis serotype 2 infection was more common than infections with Streptococcus pneumoniae and Neisseria meningitidis combined. Our results strikingly illustrate the additional diagnostic value of PCR in patients who are pretreated with antimicrobial agents and demonstrate the extremely high prevalence of S. suis infections among Vietnamese adult patients with bacterial meningitis. PMID:21767702

  9. Real-time PCR for detection of Streptococcus suis serotype 2 in cerebrospinal fluid of human patients with meningitis

    PubMed Central

    Nga, Tran Vu Thieu; Nghia, Ho Dang Trung; Tu, Le Thi Phuong; Diep, To Song; Mai, Nguyen Thi Hoang; Chau, Tran Thi Hong; Sinh, Dinh Xuan; Phu, Nguyen Hoan; Nga, Tran Thi Thu; Chau, Nguyen Van Vinh; Campbell, James; Hoa, Ngo Thi; Chinh, Nguyen Tran; Hien, Tran Tinh; Farrar, Jeremy; Schultsz, Constance

    2011-01-01

    Streptococcus suis serotype 2 is an emerging zoonotic pathogen and is the main cause of acute bacterial meningitis in adult patients in Vietnam. We developed an internally controlled real-time PCR for detection of S. suis serotype 2 in cerebrospinal fluid (CSF) samples targeted at the cps2J gene. Sensitivity and specificity in culture-confirmed clinical samples were 100%. The PCR detected S. suis serotype 2 infection in 101 of 238 (42.4%) prospectively collected CSF samples, of which 55 (23%) were culture positive. Culture-negative but PCR-positive CSF samples were significantly associated with the use of antimicrobial agents before admission. S. suis serotype 2 infection was more common than infections with Streptococcus pneumoniae and Neisseria meningitidis combined. Our results strikingly illustrate the additional diagnostic value of PCR in patients who are pretreated with antimicrobial agents and demonstrate the extremely high prevalence of S. suis infections among Vietnamese adult patients with bacterial meningitis. PMID:21767702

  10. Real-Time Polymerase Chain Reaction Detection of Angiostrongylus cantonensis DNA in Cerebrospinal Fluid from Patients with Eosinophilic Meningitis.

    PubMed

    Qvarnstrom, Yvonne; Xayavong, Maniphet; da Silva, Ana Cristina Aramburu; Park, Sarah Y; Whelen, A Christian; Calimlim, Precilia S; Sciulli, Rebecca H; Honda, Stacey A A; Higa, Karen; Kitsutani, Paul; Chea, Nora; Heng, Seng; Johnson, Stuart; Graeff-Teixeira, Carlos; Fox, LeAnne M; da Silva, Alexandre J

    2016-01-01

    Angiostrongylus cantonensis is the most common infectious cause of eosinophilic meningitis. Timely diagnosis of these infections is difficult, partly because reliable laboratory diagnostic methods are unavailable. The aim of this study was to evaluate the usefulness of a real-time polymerase chain reaction (PCR) assay for the detection of A. cantonensis DNA in human cerebrospinal fluid (CSF) specimens. A total of 49 CSF specimens from 33 patients with eosinophilic meningitis were included: A. cantonensis DNA was detected in 32 CSF specimens, from 22 patients. Four patients had intermittently positive and negative real-time PCR results on subsequent samples, indicating that the level of A. cantonensis DNA present in CSF may fluctuate during the course of the illness. Immunodiagnosis and/or supplemental PCR testing supported the real-time PCR findings for 30 patients. On the basis of these observations, this real-time PCR assay can be useful to detect A. cantonensis in the CSF from patients with eosinophilic meningitis. PMID:26526920

  11. [Concentration of tazobactam/piperacillin in the cerebrospinal fluid of patients with Haemophilus influenzae type B meningitis].

    PubMed

    Fukasawa, Chie; Hoshino, Tadashi; Kutsuna, Satoru; Sawada, Kyoko; Sato, Hiroko; Ishiwada, Naruhiko

    2013-09-01

    While the incidence of Haemophilus influenzae type b (Hib) meningitis is expected to decrease with the widespread use of the Hib vaccine, the resistance of Hib has actually increased. Therefore, selection of the initial antibiotics used for treatment must be performed with resistant bacteria, including beta-lactamase negative ampicillin resistant H. influenzae (BLNAR), in mind. Tazobactam/piperacillin (TAZ/PIPC) has a satisfactory minimum inhibitory concentration (MIC) against BLNAR and is a beta-lactamase inhibitor. Although there is no insurance coverage for its use in patients with meningitis, the penetration of TAZ/PIPC into cerebrospinal fluid (CSF) in animal experiments promises a satisfactory result, and we have been using a combination of ceftriaxone (CTRX) and TAZ/PIPC as an initial treatment and a resistant bacteria countermeasure in patients with Hib meningitis at our hospital since 2008. We examined the concentration of TAZ/PIPC in CSF to further investigate the possibility of using TAZ/PIPC as an antibiotic treatment against bacterial meningitis. In cases treated with a 1: 8 drug formulation of TAZ/PIPC against Hib meningitis at our hospital, we used the remaining portion of a CSF sample collected after the initiation of TAZ/PIPC administration and then measured the concentrations of TAZ and PIPC in the CSF. Six specimens from 5 patients between the ages of 6 and 59 months were examined. The dosage of TAZ/PIPC was 95.7-113.6 mg/kg/dose x 3 times/day, and the CSF concentrations at 0-105 minutes after the completion of the administration were 0.319-1.32 microg/mL for TAZ and 2.54-7.74 microg/mL for PIPC. With the approved dosage, the peak concentration level during the acute period indicated a sufficient CSF concentration level for the antibacterial and beta-lactamase inhibition effects against Hib. As an antibiotic treatment for H. influenzae meningitis, the combined usage of TAZ/PIPC is likely to be effective as a resistant bacteria countermeasure, in addition to third-generation cephem drugs and meropenem. PMID:24195168

  12. Pharmacokinetics of methotrexate in the cerebrospinal fluid after intracerebroventricular administration in patients with meningeal carcinomatosis and altered cerebrospinal fluid flow dynamics

    SciTech Connect

    Miller, K.T.; Wilkinson, D.S.

    1989-01-01

    Pharmacokinetic parameters of the distribution and elimination of intracerebroventricularly administered methotrexate (MTX) were evaluated in three patients with meningeal carcinomatosis. Abnormal cerebrospinal fluid (CSF) flow dynamics, which were not otherwise clinically evident, were diagnosed by 111In-diethylenetriaminepentaacetate radionuclide imaging. Alterations in CSF flow resulted in large changes in MTX distribution. Reduced cortical convexity (type III), spinal subarachnoid (type II), or ventricular (type I) CSF flow resulted in a prolongation of the single-pass mean residence time of MTX in the peripheral compartment by as much as eightfold and a reduction in intercompartmental clearance by 94-99%. Leptomeningeal carcinomatosis can affect both CSF MTX distribution and elimination, each to a different extent, within the same patient. Total MTX clearance from the CSF was reduced by 79-93% in the patients studied. A two-compartment pharmacokinetic model, with elimination occurring from the peripheral compartment, gave values for the distribution rate constant from the central to the peripheral compartment (k12), which decreased with the extent of CSF flow abnormality. However, the elimination rate constant from the peripheral compartment (k20) was reduced to an extent apparently independent of CSF flow abnormality (percentage reduction in k12 and k20, respectively: type III, 18 and 66; type II, 67 and 86; type I, 78 and 48). Inadequate distribution and locally high concentrations of MTX within the CSF may contribute to therapeutic failure and neurotoxicity. Monitoring of MTX levels in the CSF may be deceiving when samples are drawn from the site of injection, since the distribution kinetics are altered by abnormal CSF flow dynamics.

  13. Cerebrospinal fluid leak (image)

    MedlinePLUS

    Cerebrospinal fluid is the fluid found in and around the central nervous system (CNS) organs, the brain ... blows or other trauma. Inside the skull the cerebrospinal fluid is contained by the dura which covers ...

  14. High-throughput sequencing of 16S rDNA amplicons characterizes bacterial composition in cerebrospinal fluid samples from patients with purulent meningitis

    PubMed Central

    Liu, Aicui; Wang, Chao; Liang, Zhijuan; Zhou, Zhi-Wei; Wang, Lin; Ma, Qiaoli; Wang, Guowei; Zhou, Shu-Feng; Wang, Zhenhai

    2015-01-01

    Purulent meningitis (PM) is a severe infectious disease that is associated with high rates of morbidity and mortality. It has been recognized that bacterial infection is a major contributing factor to the pathogenesis of PM. However, there is a lack of information on the bacterial composition in PM, due to the low positive rate of cerebrospinal fluid bacterial culture. Herein, we aimed to discriminate and identify the main pathogens and bacterial composition in cerebrospinal fluid sample from PM patients using high-throughput sequencing approach. The cerebrospinal fluid samples were collected from 26 PM patients, and were determined as culture-negative samples. The polymerase chain reaction products of the hypervariable regions of 16S rDNA gene in these 26 samples of PM were sequenced using the 454 GS FLX system. The results showed that there were 71,440 pyrosequencing reads, of which, the predominant phyla were Proteobacteria and Firmicutes; and the predominant genera were Streptococcus, Acinetobacter, Pseudomonas, and Neisseria. The bacterial species in the cerebrospinal fluid were complex, with 61.5% of the samples presenting with mixed pathogens. A significant number of bacteria belonging to a known pathogenic potential was observed. The number of operational taxonomic units for individual samples ranged from six to 75 and there was a comparable difference in the species diversity that was calculated through alpha and beta diversity analysis. Collectively, the data show that high-throughput sequencing approach facilitates the characterization of the pathogens in cerebrospinal fluid and determine the abundance and the composition of bacteria in the cerebrospinal fluid samples of the PM patients, which may provide a better understanding of pathogens in PM and assist clinicians to make rational and effective therapeutic decisions. PMID:26300628

  15. Tubercular meningitis with hydrocephalus with HIV co-infection: role of cerebrospinal fluid diversion procedures.

    PubMed

    Sharma, Raman Mohan; Pruthi, Nupur; Arimappamagan, Arivazhagan; Somanna, Sampath; Devi, Bhagavathula Indira; Pandey, Paritosh

    2015-05-01

    OBJECT Hydrocephalus is one of the commonest complications of tubercular meningitis (TBM), and its incidence is increasing with the HIV epidemic. Literature evaluating the role of ventriculoperitoneal shunts in HIV-positive patients with TBM and their long-term prognosis is scarce. METHODS Between June 2002 and October 2012, 30 HIV-positive patients with TBM and hydrocephalus underwent ventriculoperitoneal shunt placement. Thirty age-, sex-, and grade-matched HIV-negative patients with TBM and hydrocephalus were randomly selected as the control group. Outcome was analyzed at discharge (short-term outcome) and at follow-up (long-term outcome). Univariate and multivariate analyses were performed to look for predictors of outcome; p < 0.05 was considered significant. RESULTS There were no differences in the clinical, radiological, or biochemical parameters between the 2 groups. Short-term outcome was better in the HIV-negative group (76.7% improvement) than in the HIV-positive group (70%). However, the long-term outcome in HIV-positive patients was very poor (66.7% mortality and 76.2% poor outcome) compared with HIV-negative patients (30.8% mortality and 34.6% poor outcome). Seropositivity for HIV is an independent predictor of poor outcome both in univariate and multivariate analyses (p = 0.038). However, in contrast to previous reports, of 5 patients with TBM in good Palur grades among the HIV-positive patients, 4 (80%) had good outcome following shunt placement. CONCLUSIONS The authors recommend that shunt treatment should not be performed in HIV-positive patients in poor Palur grade with hydrocephalus. A trial of external ventricular drainage should be undertaken in such patients, and shunt treatment should be performed only if there is any improvement. However, HIV-positive patients in good Palur grades should undergo VP shunt placement, as these patients have better outcomes than previously reported. PMID:25679277

  16. Diagnostic Accuracy of Presepsin (sCD14-ST) for Prediction of Bacterial Infection in Cerebrospinal Fluid Samples from Children with Suspected Bacterial Meningitis or Ventriculitis

    PubMed Central

    Stubljar, David; Kopitar, Andreja Natasa; Groselj-Grenc, Mojca; Suhadolc, Kristina; Fabjan, Teja

    2015-01-01

    Children with temporary external ventricular drains (EVD) are prone to nosocomial infections. Diagnosis of bacterial meningitis and ventriculitis in these children is challenging due to frequent blood contamination of cerebrospinal fluid (CSF) and the presence of chemical ventriculitis. The aim of this study was to compare diagnostic accuracy of presepsin (sCD14-ST), a novel biomarker of bacterial infection in CSF, to predict bacterial infection in comparison to the accuracy of established biomarkers like those demonstrated in biochemical analysis of CSF. We conducted a prospective study with 18 children with suspected bacterial meningitis or ventriculitis who had 66 episodes of disease. CSF samples were taken from external ventricular drainage. We measured presepsin in CSF, as well as CSF leukocyte count, glucose, and proteins. CSF was also taken to prove bacterial infection with culture methods or with 16S rRNA gene broad-range PCR (SepsiTest; Molzym, Germany). Infection was clinically confirmed in 57 (86%) episodes of suspected meningitis or ventriculitis. Chemical ventriculitis was diagnosed in 9 (14%) episodes of suspected meningitis or ventriculitis. Diagnostic accuracies presented as area under the curve (AUC) for sCD14-ST, leukocytes, and proteins measured in CSF were 0.877 (95% confidence interval [CI], 0.793 to 0.961), 0.798 (95% CI, 0.677 to 0.920), and 0.857 (95% CI, 0.749 to 0.964), respectively. With CSF culture, we detected bacteria in 17 samples, compared to 37 detected with broad-range PCR. It was found that presepsin was present at a significantly higher level in children with clinically proven ventriculitis than in those without meningitis or ventriculitis. Diagnostic accuracies of presepsin were superior to those of leukocytes or proteins in CSF. Presepsin-guided 16S rRNA gene PCR could be used in everyday clinical practice to improve etiological diagnosis of meningitis and ventriculitis and to prescribe more appropriate antibiotics. PMID:25653398

  17. Cerebrospinal fluid eosinophilia in a child with neuroborreliosis.

    PubMed

    Buda, Piotr; Zawadka, Konrad; Wadowska-K?opotek, Weronika; Smorczewska-Kiljan, Anna; Wieteska-Klimczak, Anna; Marczy?ska, Magdalena; Ksi??yk, Janusz

    2015-01-01

    Cerebrospinal fluid eosinophilia is rare and usually associated with eosinophilic meningitis caused by helminthic infections. It is also observed in bacterial or fungal meningitis (syphilis, tuberculosis, coccidioidomycosis), in patients with malignancies, ventriculoperitonial shunts, hypereosinophilic syndrome or allergy to some medications. Here we present a case of an 8-year-old boy admitted with fever and clinical signs of meningitis. Cerebrospinal fluid (CSF) analysis showed marked eosinophilia. Basing on further serological CSF testing the diagnosis of borreliosis was established. Cerebrospinal fluid eosinophilia in Borrelia burgdorferi infection has never been reported before. PMID:26094340

  18. Aseptic meningitis in a patient with cerebrospinal fluid anti-agalactosyl IgG antibody-positive preclinical rheumatoid arthritis: a case report.

    PubMed

    Kawabata, Yuichi; Miyaji, Yosuke; Nakano, Tatsu; Joki, Hideto; Tanaka, Fumiaki

    2015-12-23

    A 69-year-old woman presented with non-fluent aphasia, ideomotor apraxia, right hemiparesis and convulsion. Her medical history was unremarkable, and she had not suffered from arthritis. DWI and FLAIR image of brain MRI showed hyperintensities in the subarachnoid space along the left frontal and both parietal lobes, and these lesions were associated with gadolinium enhancement. The levels of serum anti-cyclic citrullinated peptide antibody, anti-agalactosyl IgG antibody and matrix metalloproteinase-3 were elevated. The results of blood cultures were negative. Cerebrospinal fluid (CSF) analysis revealed monocytic pleocytosis and negative findings for infection or malignancy. The level of anti-agalactosyl IgG antibody in CSF was elevated. The antibody index (AI) of anti-agalactosyl IgG antibody (the ratio between the CSF/serum quotient for IgG antibodies, and the CSF/serum quotient for total IgG; normal value of AI < 1.3) showed considerably high value of 8.4, indicating the intrathecal-specific antibody synthesis. As a result, the pathogenesis of her disease was consistent with rheumatoid meningitis despite lack of arthritis. After intravenous administration of methylprednisolone, her symptoms, the level of anti-agalactosyl IgG antibody in CSF, and the MRI findings were ameliorated. Anti-agalactosyl IgG antibody in the CSF was a helpful biomarker in diagnosis and assessment of the severity of rheumatoid meningitis. PMID:26511025

  19. Climate change and cerebrospinal meningitis in the Ghanaian meningitis belt.

    PubMed

    Codjoe, Samuel Nii Ardey; Nabie, Vivian Adams

    2014-07-01

    Cerebrospinal meningitis (CSM) is one of the infectious diseases likely to be affected by climate change. Although there are a few studies on the climate change-CSM nexus, none has considered perceptions of community members. However, understanding public perception in relation to a phenomenon is very significant for the design of effective communication and mitigation strategies as well as coping and adaptation strategies. This paper uses focus group discussions (FGDs) to fill this knowledge lacuna. Results show that although a few elderly participants ascribed fatal causes (disobedience to gods, ancestors, and evil spirits) to CSM infections during FGDs, majority of participants rightly linked CSM infections to dry, very hot and dusty conditions experienced during the dry season. Finally, community members use a suite of adaptation options to curb future CSM epidemics. PMID:25003550

  20. iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid reveals NELL2 as a potential diagnostic biomarker of tuberculous meningitis.

    PubMed

    Yang, Yongtao; Mu, Jun; Chen, Guanghui; Zhan, Yuan; Zhong, Jiaju; Wei, Youdong; Cheng, Ke; Qin, Bin; You, Hongmin; Xie, Peng

    2015-05-01

    Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. As TBM may result in permanent sequelae and death, rapid, accurate diagnostic tests using novel biomarkers are required for the early diagnosis and treatment of TBM. A quantitative proteomic study was therefore performed to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n=12) and healthy controls (n=12). CSF samples were labelled with iTRAQ™ and analyzed by LC-MS/MS. Gene ontology and Pathway analysis were conducted using DAVID bioinformatics resources. Neural epidermal growth factor-like like 2 (NELL2) with the largest fold-change value was selected for validation by western blotting. Proteomic phenotyping revealed over-representation in two inflammation-associated processes, complement and coagulation cascades as well as cell adhesion molecules. Western blotting showed a significant decrease in NELL2 levels in TBM subjects compared to healthy controls. The AUC analysis revealed NELL2 was able to distinguish TBM subjects from healthy controls with 83.3% sensitivity and 75% specificity. In conclusion, the results showed that CSF NELL2 is a potential diagnostic biomarker for TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other intracranial infectious diseases is required for clinical translation. PMID:25760060

  1. Survival Defects of Cryptococcus neoformans Mutants Exposed to Human Cerebrospinal Fluid Result in Attenuated Virulence in an Experimental Model of Meningitis? †

    PubMed Central

    Lee, Anthony; Toffaletti, Dena L.; Tenor, Jennifer; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur; Price, Michael; Perfect, John R.

    2010-01-01

    Cryptococcus neoformans is a fungal pathogen that encounters various microenvironments during growth in the mammalian host, including intracellular vacuoles, blood, and cerebrospinal fluid (CSF). Because the CSF is isolated by the blood-brain barrier, we hypothesize that CSF presents unique stresses that C. neoformans must overcome to establish an infection. We assayed 1,201 mutants for survival defects in growth media, saline, and human CSF. We assessed CSF-specific mutants for (i) mutant survival in both human bronchoalveolar lavage (BAL) fluid and fetal bovine serum (FBS), (ii) survival in macrophages, and (iii) virulence using both Caenorhabditis elegans and rabbit models of cryptococcosis. Thirteen mutants exhibited significant survival defects unique to CSF. The mutations of three of these mutants were recreated in the clinical serotype A strain H99: deletions of the genes for a cation ATPase transporter (ena1?), a putative NEDD8 ubiquitin-like protein (rub1?), and a phosphatidylinositol 4-kinase (pik1?). Mutant survival rates in yeast media, saline, and BAL fluid were similar to those of the wild type; however, survival in FBS was reduced but not to the levels in CSF. These mutant strains also exhibited decreased intracellular survival in macrophages, various degrees of virulence in nematodes, and severe attenuation of survival in a rabbit meningitis model. We analyzed the CSF by mass spectrometry for candidate compounds responsible for the survival defect. Our findings indicate that the genes required for C. neoformans survival in CSF ex vivo are necessary for survival and infection in this unique host environment. PMID:20696827

  2. Accuracy of Lipoarabinomannan and Xpert MTB/RIF Testing in Cerebrospinal Fluid To Diagnose Tuberculous Meningitis in an Autopsy Cohort of HIV-Infected Adults.

    PubMed

    Cox, Janneke A; Lukande, Robert L; Kalungi, Sam; Van Marck, Eric; Lammens, Martin; Van de Vijver, Koen; Kambugu, Andrew; Nelson, Ann M; Colebunders, Robert; Manabe, Yukari C

    2015-08-01

    Point-of-care tests for tuberculous meningitis (TBM) are needed. We studied the diagnostic accuracy of the lipoarabinomannan (LAM) lateral flow assay (LFA), LAM enzyme-linked immunosorbent assay (ELISA), and Xpert MTB/RIF in cerebrospinal fluid (CSF) in an autopsy cohort of Ugandan HIV-infected adults. We obtained written informed consent postmortem from the next of kin. A complete autopsy was done and CSF obtained. We performed LAM LFA (on unprepared and supernatant CSF after heating and spinning), LAM ELISA, and Xpert MTB/RIF on the CSF samples. Accuracy parameters were calculated for histopathological TBM and also for the composite standard, including Xpert MTB/RIF-positive cases. We tested CSF of 91 patients. LAM LFA had a sensitivity of 75% for definite histopathological TBM, ELISA a sensitivity of 43%, and Xpert MTB/RIF a sensitivity of 100% and specificities of 87%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 50% for definite and probable histopathological TBM, ELISA a sensitivity of 38%, and Xpert MTB/RIF a sensitivity of 86% and specificities of 70%, 91%, and 87%, respectively. LAM LFA had a sensitivity of 68% for the composite standard and ELISA a sensitivity of 48% and specificities of 78% and 98%, respectively. The rapid diagnostic tests detected TBM in 22% to 78% of patients not on anti-TB treatment. Point-of-care tests have high accuracy in diagnosis of TBM in deceased HIV-infected adults. LAM LFA in CSF is a useful additional diagnostic tool. PMID:26063865

  3. Cerebrospinal fluid culture

    MedlinePLUS

    If bacteria are present, you may have bacterial meningitis . Other possible infections include tuberculosis and fungal infections. ... the infection is contagious, unless it is meningococcal meningitis. It may also include: Aseptic meningitis Cryptococcosis

  4. Chronic Meningitis

    MedlinePLUS

    ... spinal cord (meninges) and of the fluid-filled space between the meninges (subarachnoid space) when it lasts 4 weeks or longer (see ... cerebrospinal fluid. The cause is treated. The subarachnoid space is located between the middle layer and the ...

  5. Aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in Ghana

    PubMed Central

    2012-01-01

    Abstracts Background Meningitis is an important cause of morbidity and mortality in low-resource settings. In sub-Saharan Africa, the meningitis belt has been characterized by particularly high and seasonal incidences of bacterial meningitis extending throughout life. Despite the progress being made in treating the condition, the mortality rates continue to be high, ranging between 2% and 30% globally. In Ghana, the mortality rate of meningitis has been estimated to range from 36% to 50%. However little information is available on the pathogens contributing to meningitis and their antimicrobial susceptibilities. Updated information is essential to adjust the recommendations for empirical treatment or prevention of meningitis which could have immense implications for local and global health. Methods We retrospectively reviewed laboratory records of all patients suspected of bacterial meningitis who underwent a lumbar puncture from January 1, 2008 to December 31, 2010. Data were retrieved from laboratory record books and double entered into a Microsoft® excel spreadsheet. Results Records of 4,955 cerebrospinal fluid samples were analysed. Of these, 163 (3.3%, 95%CI: 2.8% to 3.8%) were confirmed meningitis and 106 (2.1%, 95%CI: 1.7% to 2.6%) were probable meningitis cases. Confirmed meningitis cases were made up of 117 (71.8%) culture positive bacteria, 19 (11.7%) culture positive Cryptococcus neoformans and 27(16.6%) Gram positive bacteria with negative culture. The most prevalent bacteria was Streptococcus pneumoniae 91 (77.7%), followed by E.coli 4 (3.4%), Salmonella species 4 (3.4%), Neisseria meningitidis 3 (2.5%), Pseudomonas species 3(2.5%) and others. Pneumococcal isolates susceptibility to penicillin, chloramphenicol and ceftriaxone were 98.9% (95%CI: 94.0% to 100.0%), 83.0% (95%CI: 73.4% to 90.1%) and 100.0% (95%CI: 95.8% to 100.0%) respectively. Conclusion Streptococcus pneumoniae is an important cause of meningitis among all age groups and its susceptibility to penicillin and ceftriaxone still remains very high. Ghanaians of all ages and possibly other developing countries in the meningitis belt could benefit from the use of the pneumococcal vaccine. Other bacterial and fungal pathogens should also be considered in the management of patients presenting with meningitis. PMID:23035960

  6. Human cytomegalovirus DNA in cerebrospinal fluid.

    PubMed Central

    Kohyama, J; Kajiwara, M; Shimohira, M; Iwakawa, Y; Okawa, H

    1994-01-01

    To determine the involvement of human cytomegalovirus (CMV) in conditions of neurological impairment, detection of CMV DNA was attempted in cerebrospinal fluid obtained from 45 neurologically affected children aged from 1 month to 17 years by means of the polymerase chain reaction. Four patients (congenital CMV encephalopathy with West's syndrome, acute encephalitis, chronic epileptic encephalopathy, and lissencephaly) had CMV DNA in their cerebrospinal fluid. CMV DNA was absent in the cerebrospinal fluid of 11 neurologically unaffected controls aged from 1 month to 11 years. Three patients with acute CMV hepatitis had no CMV DNA in their cerebrospinal fluid. Among the four patients who had CMV DNA in their cerebrospinal fluid, two did not excrete CMV DNA or CMV antigen in the urine. The possible pathogenetic significance of CMV DNA in the cerebrospinal fluid is discussed. By applying the polymerase chain reaction to cerebrospinal fluid, the mode of brain invasion by CMV can be clarified further. Images PMID:7826111

  7. [Early diagnosis, early therapy and prognosis of epidemic cerebrospinal meningitis].

    PubMed

    Lobzin, V S; Al'tfel'd, Iu S; Lobzin, Iu V

    1976-09-01

    The authors convened a special study for purposes of determining early signs of epidemic cerebrospinal meningitis and for the dependence of the prognosis from early etiotropic and pathogenetic therapy. On the basis of a study of 93 cases criteria of early diagnosis are being given. Unlike the data in literature, in 60.2% of the cases it was possible to initiate treatment during the first hours of the disease and in 94.6% -- not later than 48 hours. In most of the cases the disease had a grave course. Changed consciousness was observed in 55.9%, an increased amount of protein in the CSF -- in 58%. In 8 cases there was a syndrome of acute renal insufficiency. Despite these facts all the patients recovered. The authors come to the conclusion that prognosis may be significantly improved in cases of early diagnosis (during the first hours), intensive penicillin therapy (both intravenously and kanamicin into the carotid artery). The authors suggest that during reconvalescence it is feasible to prescribe resolving (pyrogenal lydase) and general therapy. PMID:1015133

  8. The Maze of the Cerebrospinal Fluid Discovery

    PubMed Central

    2013-01-01

    The author analyzes a historical, long, and tortuous way to discover the cerebrospinal fluid. At least 35 physicians and anatomists described in the text have laid the fundamentals of recognition of this biological fluid's presence. On the basis of crucial anatomical, experimental, and clinical works there are four greatest physicians who should be considered as equal cerebrospinal fluid's discoverers: Egyptian Imhotep, Venetian Nicolo Massa, Italian Domenico Felice Cotugno, and French François Magendie. PMID:24396600

  9. Confocal Raman microscopy of pathologic cells in cerebrospinal fluid

    NASA Astrophysics Data System (ADS)

    Gonchukov, S. A.; Lonkina, T. V.; Minaeva, S. A.; Sundukov, A. V.; Migmanov, T. E.; Lademann, J.; Darvin, M. E.; Bagratashvili, V. N.

    2014-01-01

    In this work, the spatial localization of leucocytes, bacteria, and erythrocytes in the crystal pattern of a dried droplet of cerebrospinal fluid (CSF) is established. Characteristic lines are detected and identified in the Raman spectrum of the CSF that point to the presence of pathologic cells therein and can be used in a timely way to diagnose meningitis, the spectroscopic sample preparation procedure being simple enough. A dry CSF sample retains its characteristic spectral features for no less than three days, which is important for its safe keeping and transportation, and also for the computer processing of its spectra.

  10. [Cerebrospinal fluid as informative source of the brain].

    PubMed

    Ohtsuka, C

    1991-03-01

    The examination of cerebrospinal fluid has provided useful information for diagnosis of CNS infections. The progress of analytical technology has brought the possibility to detect very small amounts of chemical substances. I thought that new information from brain should be obtained by using modern analytical technology for several substances in CSF. Free amino acid pattern, glutamine, homocarnosine, glutamic acid decarboxylase (GAD), neuron specific enolase (NSE) and 2',5'-oligoadenylic acid synthetase (2-5 A) in CSF have been examined for information of brain injury and dysfunctions. The results are as follows. 1) The individual difference and constancy of free amino acid pattern in CSF were found in children without any neurological diseases. 2) The levels of free amino acids in CSF increased in the acute phase of bacterial meningitis. 3) High levels of glutamine in CSF of children with acute bacterial meningitis were normalized during the recovery phase. 4) A marked imbalance of free amino acids in CSF was found in children with Lennox-Gastaut syndrome. 5) A decrease of homocarnosine levels in CSF was related with the degree of unconsciousness in children suffering from neurological diseases. 6) High GAD activities in CSF were observed in the acute phase of aseptic meningitis and after intrathecal injection of methotrexate for the therapy against meningeal leukemia. 7) High NSE activities in CSF were found in the acute phase of bacterial meningitis, intracranial hemorrhage, encephalopathy and encephalitis. 8) High 2-5A activities CSF were measured in the acute phase of mumps meningitis with subsequent decreases during the recovery phase. These results suggest that several substances in CSF are useful as markers of brain injury and dysfunction. PMID:2012695

  11. Clinical implications of acute cerebrospinal fluid changes following iophendylate myelography.

    PubMed

    Mehta, H J; Ramakantan, R; Piparia, D H; Hande, A M; Goel, A; Satoskar, A R; Dastur, F D

    1992-01-01

    Clinical features and serial cerebrospinal fluid (CSF) samples of 50 patients who underwent myelography with iophendylate were studied. Forty two patients (84%) developed one or more features suggestive of meningism lasting for 2-4 days. There was significant rise in the average (mean) CSF counts from 9.81 in the premyelogram sample to 532.6 at the end of 24 hours (p less than 0.001). Both neutrophil and lymphocyte (p less than 000) count increased. At the end of one week, there was significant decrease of total cells in the CSF to 204 (p less than 0.001). Both, neutrophils and lymphocytes decreased. There was significant rise in total proteins in the 24 hours sample, but the fall at one week was not significant statistically. The sugar and chloride values did not change significantly. All CSF samples were negative for bacterial cultures. In conclusion, a significant proportion of the patients undergoing iophendylate myelography develop clinical features suggestive of meningeal irritation and change in the CSF fractions suggestive of meningitis: however these changes are transient and do not warrant institution of chemotherapy or steroids. PMID:1512716

  12. Beta2-Microglobulin as a Diagnostic Marker in Cerebrospinal Fluid: A Follow-Up Study

    PubMed Central

    Svato?ová, Jana; Bo?ecká, Klára; Adam, Pavel; Lánská, V?ra

    2014-01-01

    Beta2-Microglobulin (?2-m) is a low molecular weight protein occurring in all body fluids. Its concentration increases in various pathologies. Increased values in cerebrospinal fluid (CSF) are ascribed to an activation of immune system. Using immunoturbidimetry, we examined concentrations of beta2-microglobulin in cerebrospinal fluid in a large group of 6274 patients with defined neurological diseases. Cell counts, total protein, albumin, glucose, lactic acid, immunoglobulins concentrations, and isofocusing (IEF) were also evaluated. We found substantial changes of CSF ?2-m concentrations in purulent meningitis, leptomeningeal metastasis, viral meningitis/encephalitis, and neuroborreliosis, while in multiple sclerosis these changes were not significant. Intrathecal synthesis and immune activation were present in these clinical entities. A new normative study enables better understanding of beta2-microglobulin behavior in CSF. PMID:24895473

  13. Endonasal Endoscopic Closure of Cerebrospinal Fluid Rhinorrhea

    PubMed Central

    Schmerber, S.; Righini, Ch.; Lavielle, J.-P.; Passagia, J.-G.; Reyt, E.

    2001-01-01

    The authors review their experience with endoscopic repair of skull base defects associated with cerebrospinal fluid (CSF) rhinorrhea involving the paranasal sinuses. A total of 22 patients was treated endoscopically between 1992 and 1998. The repair method consisted of closure of the CSF fistula with a free autologous abdominal fat graft and fibrin glue, supported with a sheet of silastic. The primary closure rate was 82% (18/22), and the overall closure rate was 95.5% (21/22) without recurrence or complications within an average follow-up of 5 years (14-83 months). A single patient still complains of cerebrospinal rhinorrhea, although this was never proved by any clinical, endoscopic, or biological (?2-transferrin) examination. The repair of ethmoidal-sphenoidal cerebrospinal fluid fistulae by endonasal endoscopic surgery is an excellent technique, both safe and effective. Fat is a material of choice, as it is tight and resists infection well. The technique and indications for endoscopic management of cerebrospinal fluid leaks are discussed. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5 PMID:17167603

  14. Serum and cerebrospinal fluid levels of colistin in pediatric patients.

    PubMed

    Antachopoulos, Charalampos; Karvanen, Matti; Iosifidis, Elias; Jansson, Britt; Plachouras, Diamantis; Cars, Otto; Roilides, Emmanuel

    2010-09-01

    Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 microg/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 microg/ml but increased in the presence of meningitis (approximately 0.5 microg/ml or 34 to 67% of serum levels). PMID:20585114

  15. Serum and Cerebrospinal Fluid Levels of Colistin in Pediatric Patients?

    PubMed Central

    Antachopoulos, Charalampos; Karvanen, Matti; Iosifidis, Elias; Jansson, Britt; Plachouras, Diamantis; Cars, Otto; Roilides, Emmanuel

    2010-01-01

    Using a liquid chromatography-tandem mass spectrometry method, the serum and cerebrospinal fluid (CSF) concentrations of colistin were determined in patients aged 1 months to 14 years receiving intravenous colistimethate sodium (60,000 to 225,000 IU/kg of body weight/day). Only in one of five courses studied (a 14-year-old receiving 225,000 IU/kg/day) did serum concentrations exceed the 2 ?g/ml CLSI/EUCAST breakpoint defining susceptibility to colistin for Pseudomonas and Acinetobacter. CSF colistin concentrations were <0.2 ?g/ml but increased in the presence of meningitis (?0.5 ?g/ml or 34 to 67% of serum levels). PMID:20585114

  16. Epidural cerebrospinal fluid collection after lumbar puncture.

    PubMed

    Aronson, Paul L; Zonfrillo, Mark R

    2009-07-01

    Lumbar puncture is a common procedure in the emergency department. Cerebrospinal fluid (CSF) leak through a dural tear can cause transient side effects including headache and backache, although more severe symptoms may occur. These CSF collections can be managed nonoperatively without any neurologic sequelae. We report a patient with a symptomatic epidural CSF collection after diagnostic lumbar puncture, followed by a brief review of the literature including discussion of techniques that can reduce CSF leak. PMID:19606006

  17. A Case of Cerebrospinal Fluid Rhinorrhoea: A Surgical Challenge

    PubMed Central

    R, Sumitha; Hari, P M; Kumar, S Ramya; Hariprasad, R

    2013-01-01

    CEREBROSPINAL FLUID rhinorrhoea is defined as the leakage of CEREBROSPINAL FLUID through the nose due to communication between nasal cavity and Sub-arachnoid space. It occurs due to breach in 4 layers – mucosa of the nose and PNS, skull base, Duramater, Subarachnoid membrane. With the advent of nasal endoscope and advancement in technology, Endoscopic Endonasal closure of CEREBROSPINAL FLUID leak has reached tremendous heights due to exact localization and precise placement of graft. In this article, we are publishing a case report of Non-traumatic normal pressure CEREBROSPINAL FLUID leak of more than 1.5cm in size which was successfully closed Endoscopically by multilayered technique PMID:23998089

  18. Cerebrospinal fluid pressure and the eye.

    PubMed

    Morgan, William H; Balaratnasingam, Chandrakumar; Lind, Christopher R P; Colley, Steve; Kang, Min H; House, Philip H; Yu, Dao-Yi

    2016-01-01

    Cerebrospinal fluid pressure (CSFP) interacts with intraocular pressure (IOP) and blood pressure to exert a major influence upon the eye, particularly the optic nerve head region. There is increased interest regarding the influence of CSFP upon disorders affecting this region, in particular glaucoma and idiopathic intracranial hypertension. Additionally, a high proportion of astronauts develop features similar to idiopathic intracranial hypertension that persist for years after returning to Earth. The factors that affect the CSFP influence upon the optic nerve and globe are likely to influence the outcome of various ophthalmic disorders. PMID:25877896

  19. High risk of cerebrospinal fluid leakage in surgery of a rare primary intraosseous cavernous hemangioma of the clivus showing meningeal infiltration: A case report and review of the literature

    PubMed Central

    Serrano, Lucas; Archavlis, Eleftherios; Januschek, Elke; Ulrich, Peter T.

    2015-01-01

    Background: Primary intraosseous cavernous hemangiomas (PICH) of the skull represent an infrequent bone tumor. Although some rare cases of PICHs located in the skull base have been published, to our concern only three cases have been reported in the English literature of PICHs arising within the clivus. Case Description: We present the case of a patient presenting an isolated abducens paresis due to a rare PICH of the clivus showing also an unusual destruction of the inner table as well as infiltration of the dura mater. Due to this uncommon infiltrative pattern of an otherwise expected intraosseous tumor, a cerebrospinal fluid (CSF)-fistula occurred while performing a transnasal biopsy. The patient recovered successfully without need of lumbar drainage or re-surgery. Additionally, intratumoral decompression was sufficient to relief the abducens paresis. Conclusions: Our case provides new and meaningful information about clinical features as well as growth pattern of these rare clival tumors. We also discuss the importance of knowing these peculiarities before surgery in order to plan the optimal operative management as well as to avoid complications while approaching PICHs localized in such a delicate cranial region. PMID:25949853

  20. CEREBROSPINAL FLUID STASIS AND ITS CLINICAL SIGNIFICANCE

    PubMed Central

    Whedon, James M.; Glassey, Donald

    2010-01-01

    We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste products of cellular metabolism, and transports hormones, neurotransmitters, releasing factors, and other neuropeptides throughout the CNS. Physiologic impedance or cessation of CSF flow may occur commonly in the absence of degenerative changes or pathology and may compromise the normal physiologic functions of the CSF. CSF appears to be particularly prone to stasis within the spinal canal. CSF stasis may be associated with adverse mechanical cord tension, vertebral subluxation syndrome, reduced cranial rhythmic impulse, and restricted respiratory function. Increased sympathetic tone, facilitated spinal segments, dural tension, and decreased CSF flow have been described as closely related aspects of an overall pattern of structural and energetic dysfunction in the axial skeleton and CNS. Therapies directed at affecting CSF flow include osteopathic care (especially cranial manipulation), craniosacral therapy, chiropractic adjustment of the spine and cranium, Network Care (formerly Network Chiropractic), massage therapy (including lymphatic drainage techniques), yoga, therapeutic breathwork, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted. PMID:19472865

  1. Novel Cyclovirus in Human Cerebrospinal Fluid, Malawi, 2010–2011

    PubMed Central

    Zijlstra, Ed E; van Hellemond, Jaap J.; Schapendonk, Claudia M.E.; Bodewes, Rogier; Schürch, Anita C.; Haagmans, Bart L.; Osterhaus, Albert D.M.E.

    2013-01-01

    To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism. PMID:23968557

  2. Observations on an Epidemic of Cerebrospinal Meningitis in Cyprus and the Record of a Prophylactic Experiment

    PubMed Central

    Maclean, I. H.; Bevan, C. E.

    1939-01-01

    After a lapse of twenty-five years cerebrospinal meningitis appeared again in epidemic from during 1936-37. A prophylactic inoculation experiment was undertaken during the autumn of 1937, a few months before the second epidemic season was due to begin. Season 1936-37—836 cases—284 deaths. Season 1937-38 (after inoculation)—298 cases—81 deaths. Season 1938-39—122 cases—51 deaths (to end of May, 1939). During the second season conditions were suitable for the continuance of the epidemic. We do not think that we obtained a false result by inoculating on a waning epidemic. Our results are inconclusive because owing to the sharp decline in the morbidity neither control nor inoculated groups were fully at risk. But our results are good enough to recommend a further trial of prophylaxis in future epidemics. The percentage of the population inoculated is an important factor. The aim should be 100%. The experiment should aim at controlling not only the meningococcal carrier rate but also the general catarrh rate. We suggest that the rapid passage of the meningoccocus in association with an epidemic of nasopharyngeal catarrh raises the virulence of the meningococcus. As the opportunity of a second experience in the prevention of cerebrospinal meningitis by prophylactic inoculation seldom occurs to an individual, we take this chance of making recommendations for guiding future experiments. PMID:19992142

  3. Volumetric relief map for intracranial cerebrospinal fluid distribution analysis.

    PubMed

    Lebret, Alain; Kenmochi, Yukiko; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe; Petit, Éric

    2015-09-01

    Cerebrospinal fluid imaging plays a significant role in the clinical diagnosis of brain disorders, such as hydrocephalus and Alzheimer's disease. While three-dimensional images of cerebrospinal fluid are very detailed, the complex structures they contain can be time-consuming and laborious to interpret. This paper presents a simple technique that represents the intracranial cerebrospinal fluid distribution as a two-dimensional image in such a way that the total fluid volume is preserved. We call this a volumetric relief map, and show its effectiveness in a characterization and analysis of fluid distributions and networks in hydrocephalus patients and healthy adults. PMID:26125975

  4. Cerebrospinal fluid PCR analysis and biochemistry in bodies with severe decomposition.

    PubMed

    Palmiere, Cristian; Vanhaebost, Jessica; Ventura, Francesco; Bonsignore, Alessandro; Bonetti, Luca Reggiani

    2015-02-01

    The aim of this study was to assess whether Neisseria meningitidis, Listeria monocytogenes, Streptococcus pneumoniae and Haemophilus influenzae can be identified using the polymerase chain reaction technique in the cerebrospinal fluid of severely decomposed bodies with known, noninfectious causes of death or whether postmortem changes can lead to false positive results and thus erroneous diagnostic information. Biochemical investigations, postmortem bacteriology and real-time polymerase chain reaction analysis in cerebrospinal fluid were performed in a series of medico-legal autopsies that included noninfectious causes of death with decomposition, bacterial meningitis without decomposition, bacterial meningitis with decomposition, low respiratory tract infections with decomposition and abdominal infections with decomposition. In noninfectious causes of death with decomposition, postmortem investigations failed to reveal results consistent with generalized inflammation or bacterial infections at the time of death. Real-time polymerase chain reaction analysis in cerebrospinal fluid did not identify the studied bacteria in any of these cases. The results of this study highlight the usefulness of molecular approaches in bacteriology as well as the use of alternative biological samples in postmortem biochemistry in order to obtain suitable information even in corpses with severe decompositional changes. PMID:25623190

  5. A new look at cerebrospinal fluid circulation

    PubMed Central

    2014-01-01

    According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation. PMID:24817998

  6. Characterization of individual mouse cerebrospinal fluid proteomes

    SciTech Connect

    Smith, Jeffrey S.; Angel, Thomas E.; Chavkin, Charles; Orton, Daniel J.; Moore, Ronald J.; Smith, Richard D.

    2014-03-20

    Analysis of cerebrospinal fluid (CSF) offers key insight into the status of the central nervous system. Characterization of murine CSF proteomes can provide a valuable resource for studying central nervous system injury and disease in animal models. However, the small volume of CSF in mice has thus far limited individual mouse proteome characterization. Through non-terminal CSF extractions in C57Bl/6 mice and high-resolution liquid chromatography-mass spectrometry analysis of individual murine samples, we report the most comprehensive proteome characterization of individual murine CSF to date. Utilizing stringent protein inclusion criteria that required the identification of at least two unique peptides (1% false discovery rate at the peptide level) we identified a total of 566 unique proteins, including 128 proteins from three individual CSF samples that have been previously identified in brain tissue. Our methods and analysis provide a mechanism for individual murine CSF proteome analysis.

  7. Imhotep and the Discovery of Cerebrospinal Fluid

    PubMed Central

    Blomstedt, Patric

    2014-01-01

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

  8. Imhotep and the discovery of cerebrospinal fluid.

    PubMed

    Blomstedt, Patric

    2014-01-01

    Herbowski (2013) suggested recently the Egyptian Imhotep from the 3rd dynasty in Egypt to be the discoverer of cerebrospinal fluid. There are, however, no sources within the first 2000 years after Imhotep suggesting him to be in any way connected with the field of medicine. Over the course of three millennia Imhotep evolves into the sage who besides architecture also masters the arts of medicine, magic, astronomy, and astrology, at the same time as him being transformed from man to demi-God, and finally to a God. The identification of Imhotep as a doctor has thus little to do with facts and it is unlikely that he had anything to do with the Edwin-Smith papyrus from a much later period where CSF is first mentioned. PMID:24744920

  9. Endogenous benzodiazepine ligands in human cerebrospinal fluid.

    PubMed

    Deckert, J; Kuhn, W; Przuntek, H

    1984-01-01

    Human cerebrospinal fluid was chromatographed on Bio-Gel P-4. Fractions containing material with molecular weights less than 4000 Dalton were pooled and further fractionated by high pressure liquid chromatography on an UltroPack TSK column G 2000 SW. At least three peaks, which were free of salt and GABA, were shown to displace (3H)-diazepam in the receptor-binding assay. Two of these peaks inhibited diazepam-binding competitively as shown by Lineweaver-Burke and displacement analysis. Their activity could be enhanced by the addition of GABA to the assay mixture. Incubation of these two peaks with various enzymes indicated that at least part of the activity of the second peak is due to a peptide. PMID:6089149

  10. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  11. Cerebrospinal Fluid Corticotropin and Cortisol Are Reduced in Infantile Spasms

    PubMed Central

    Baram, Tallie Z.; Mitchell, Wendy G.; Hanson, Rebecca A.; Snead, O. Carter; Horton, E.J.

    2012-01-01

    Infantile spasms respond to ACTH, and levels of the hormone in cerebrospinal fluid of untreated infants with this disorder were found to be lower than in age-matched controls. In this study we analyzed cerebrospinal fluid Cortisol and ACTH using improved immunoassays in a larger cohort of infants with infantile spasms. Analysis of 20 patients and 15 age-matched controls revealed significantly lower levels of both ACTH and Cortisol in the cerebrospinal fluid. These data, combined with the efficacy of ACTH and glucocorticoids for infantile spasms, support an involvement of the brain-adrenal-axis in this disorder. PMID:8534274

  12. Meningitis

    MedlinePLUS

    ... Your Best Self Smart Snacking Losing Weight Safely Meningitis KidsHealth > Teens > Infections > Bacterial & Viral Infections > Meningitis Print ... news. However, it's also pretty rare. What Is Meningitis? Meningitis is inflammation of membranes around the brain ...

  13. Cerebrospinal fluid composition modifications after neuroendoscopic procedures.

    PubMed

    Salvador, L; Valero, R; Carrero, E; Caral, L; Fernández, S; Marín, J L; Ferrer, E; Fábregas, N

    2007-02-01

    Normal saline solution is currently used as the ventricular irrigation fluid during neuroendoscopic procedures. The aim of this study is to determine the alterations in the cerebrospinal fluid (CSF) composition after neuroendoscopic interventions. Twenty nine patients who underwent a neuroendoscopic procedure under general anaesthesia were studied. Temperature inside the cerebral ventricle was measured and samples of CSF were taken to determinate oxygen and carbon dioxide partial pressures, pH, base excess, ionised calcium, standard bicarbonate, glucose, sodium, potassium, magnesium, total calcium, proteins, chlorine and osmolality before initiating the irrigation and after the neuronavigation. Patient demographics, neuronavigation time, total fluid volume used and temperature of the irrigation solution and complications that appeared in the first 24 hours were collected. Mean age of the patients was 42+/-18 years. The mean neuronavigation time was 21.5+/-15.4 minutes. The mean amount of saline solution used for irrigation was 919.6+/-994.7 mL. All the values studied in the CSF, except osmolality, showed significant variations. There was a significant correlation between the CSF variation of pH, oxygen and carbon dioxide partial pressures, base excess, standard bicarbonate, glucose and total calcium with respect to the total volume of irrigation solution, but not with respect to the neuronavigation time. A cut-off point of 500 mL of irrigation solution (sensitivity 0.7; specificity 0.87) was related with a CSF pH decrease greater than 0.2. The use of saline as irrigation solution during neuroendoscopic procedures produces important changes in CSF. PMID:17546545

  14. Cerebrospinal fluid biomarkers in Progranulin mutations carriers.

    PubMed

    Carecchio, Miryam; Fenoglio, Chiara; Cortini, Francesca; Comi, Cristoforo; Benussi, Luisa; Ghidoni, Roberta; Borroni, Barbara; De Riz, Milena; Serpente, Maria; Cantoni, Claudia; Franceschi, Massimo; Albertini, Valentina; Monaco, Francesco; Rainero, Innocenzo; Binetti, Giuliano; Padovani, Alessandro; Bresolin, Nereo; Scarpini, Elio; Galimberti, Daniela

    2011-01-01

    Cerebrospinal fluid (CSF) biomarkers (A?????, total tau, P-181 tau) are currently used to support a clinical diagnosis of Alzheimer's disease (AD). The CSF profile in frontotemporal lobar degeneration (FTLD) caused by Progranulin (GRN) mutation is unknown. We assessed CSF biomarkers in 145 AD, 140 FTLD (20 GRN positive, 120 GRN negative) patients, and 38 controls. Taking into account the reference values used in clinical practice, GRN mutation carriers and controls did not differ significantly for any biomarker, whereas GRN negative FTLD patients had higher tau levels than controls (p < 0.001) and patients carrying GRN Thr272fs mutation (p = 0.033, Chi-Square test). Comparing CSF biomarkers mean values among groups, total tau was significantly increased in GRN negative FTLD and in mutation carriers compared with controls (p < 0.001). P-181 tau CSF was increased in AD patients and in GRN negative FTLD compared with controls (p < 0.001), but not in 17 patients carrying the Thr272fs mutation. 88.2% of mutation carriers had normal CSF tau, despite the neurodegenerative nature of FTLD. Our results suggest that GRN mutation carriers have normal or borderline CSF biomarkers. In patients with an AD-like phenotype but normal or borderline CSF biomarkers, a diagnosis of FTLD-U caused by GRN mutations should be considered. PMID:21891865

  15. Spontaneous cerebrospinal fluid leakage through fistulas at the clivus repaired with endoscopic endonasal approach

    PubMed Central

    Hayashi, Yasuhiko; Iwato, Masayuki; Kita, Daisuke; Fukui, Issei

    2015-01-01

    Background: Causes of cerebrospinal fluid (CSF) leakage are primarily traumatic or iatrogenic in origin. In contrast, spontaneous CSF leakage is somewhat rare, and detection of the fistula can be challenging. Meningitis associated with CSF leakage can be life threatening. It is therefore critical to surgically repair the fistula once the underlying cause has been accurately identified. Spontaneous CSF leakage located at the clivus is an extremely rare condition. Case Description: We present the case of a 38-year-old male with sudden-onset headache and subsequent disturbances of consciousness. The patient was diagnosed with severe meningitis caused by CSF leakage through fistulas at the clivus, which were clearly identified on dynamic imaging using high-resolution computed tomography (CT) with intrathecal injection of contrast medium. After the meningitis was resolved, successful endoscopic repair of the CSF fistula with autologous materials was performed. There has been no recurrence of meningitis for 5 years. Conclusion: Spontaneous CSF leakage at the clivus is an extremely rare condition. High-resolution CT cisternogram could accurately detect CSF leakage through the clivus. A transnasal endoscopic approach was a useful and reliable method of repairing the fistula at the clivus. PMID:26110086

  16. Quantitative proteomics of delirium cerebrospinal fluid

    PubMed Central

    Poljak, A; Hill, M; Hall, R J; MacLullich, A M; Raftery, M J; Tai, J; Yan, S; Caplan, G A

    2014-01-01

    Delirium is a common cause and complication of hospitalization in older people, being associated with higher risk of future dementia and progression of existing dementia. However relatively little data are available on which biochemical pathways are dysregulated in the brain during delirium episodes, whether there are protein expression changes common among delirium subjects and whether there are any changes which correlate with the severity of delirium. We now present the first proteomic analysis of delirium cerebrospinal fluid (CSF), and one of few studies exploring protein expression changes in delirium. More than 270 proteins were identified in two delirium cohorts, 16 of which were dysregulated in at least 8 of 17 delirium subjects compared with a mild Alzheimer's disease neurological control group, and 31 proteins were significantly correlated with cognitive scores (mini-mental state exam and acute physiology and chronic health evaluation III). Bioinformatics analyses revealed expression changes in several protein family groups, including apolipoproteins, secretogranins/chromogranins, clotting/fibrinolysis factors, serine protease inhibitors and acute-phase response elements. These data not only provide confirmatory evidence that the inflammatory response is a component of delirium, but also reveal dysregulation of protein expression in a number of novel and unexpected clusters of proteins, in particular the granins. Another surprising outcome of this work is the level of similarity of CSF protein profiles in delirium patients, given the diversity of causes of this syndrome. These data provide additional elements for consideration in the pathophysiology of delirium as well as potential biomarker candidates for delirium diagnosis. PMID:25369144

  17. Meningitis

    MedlinePLUS

    Meningitis is an infection of the membranes covering the brain and spinal cord. This covering is called ... The most common causes of meningitis are viral infections. These ... meningitis infections are very serious. They may result in ...

  18. Meningitis

    MedlinePLUS

    ... Digestive System How the Body Works Main Page Meningitis KidsHealth > Kids > Health Problems > Brain & Nervous System > Meningitis ... there are ways to prevent it. What Is Meningitis? The central nervous system (brain and spinal cord) ...

  19. [Ion concentration in the cerebrospinal fluid in multiple sclerosis].

    PubMed

    Linke, E; Winnefeld, K; Dawczynski, H

    1977-08-01

    The concentrations of electrolytes Na, K, Ca, Mg, and Cl and trace elements Cu and Zn were determined in the lumbar cerebrospinal fluids of forty patients with multiple sclerosis. Metal ion concentrations were measured using atomic absorption spectroscopy and flame photometry, respectively. Compared with corresponding values obtained from a control group, statistically significant increases in concentration of Na, Cl, Ca, and Zn have been found. Also reported are the results of determinations of ion concentrations in cerebrospinal fluids obtained from patients suffering from diseases other than multiple sclerosis. Possible causes of deviations from the norm are discussed. PMID:928567

  20. Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects.

    PubMed

    Toledo, Jon B; Zetterberg, Henrik; van Harten, Argonde C; Glodzik, Lidia; Martinez-Lage, Pablo; Bocchio-Chiavetto, Luisella; Rami, Lorena; Hansson, Oskar; Sperling, Reisa; Engelborghs, Sebastiaan; Osorio, Ricardo S; Vanderstichele, Hugo; Vandijck, Manu; Hampel, Harald; Teipl, Stefan; Moghekar, Abhay; Albert, Marilyn; Hu, William T; Monge Argilés, Jose A; Gorostidi, Ana; Teunissen, Charlotte E; De Deyn, Peter P; Hyman, Bradley T; Molinuevo, Jose L; Frisoni, Giovanni B; Linazasoro, Gurutz; de Leon, Mony J; van der Flier, Wiesje M; Scheltens, Philip; Blennow, Kaj; Shaw, Leslie M; Trojanowski, John Q

    2015-09-01

    In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-?1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-?1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-? amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-?1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ?4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-?1-42 values and APOE ?2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-?1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-?1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology. PMID:26220940

  1. More Than the Brain's Drain: Does Cerebrospinal Fluid Help the Brain Convey Messages?

    ERIC Educational Resources Information Center

    Travis, John

    1999-01-01

    Examines the role of cerebrospinal fluid (CSF), a clear, colorless liquid that constantly bathes the brain and spinal cord. Scientists argue that cerebrospinal fluid carries important signals for sleep, appetite, and sex. Evaluates past and current research documenting the purpose of cerebrospinal fluid in the brain. (CCM)

  2. Secretion into the cerebrospinal fluid by caudal neurosecretory neurons.

    PubMed

    Gridberg, G; Nishioka, R S

    1966-04-01

    Neurons of the regenerating caudal neurosecretory system of Tilapia mossambica and of the normal system of Albula vulpes send processes into the central canal of the spinal cord. Evidence for appreciable release of secretion into the cerebrospinal fluid from these processes has been obtainied with both light and electron microscopes. PMID:5910018

  3. Langerhans cell histiocytosis infiltration in cerebrospinal fluid: a case report.

    PubMed

    Ghosal, N; Kapila, K; Kakkar, S; Verma, K

    2001-02-01

    Langerhans cell histiocytosis (LCH) is a disease of unknown etiology characterized by a proliferation of histiocytic cells resembling the integumentary cells bearing the name of Langerhans cells. LCH can be unifocal or multifocal, with one- or many-organ involvement. We present a case of LCH diagnosed in the cerebrospinal fluid of a patient with generalized lymphadenopathy and central nervous system involvement. PMID:11169892

  4. Japanese Encephalitis Virus in Meningitis Patients, Japan

    PubMed Central

    Ito, Mikako; Takao, Shinichi; Shimazu, Yukie; Fukuda, Shinji; Miyazaki, Kazuo; Kurane, Ichiro; Takasaki, Tomohiko

    2005-01-01

    Cerebrospinal fluid specimens from 57 patients diagnosed with meningitis were tested for Japanese encephalitis virus. Total RNA was extracted from the specimens and amplified. Two products had highest homology with Nakayama strain and 2 with Ishikawa strain. Results suggest that Japanese encephalitis virus causes some aseptic meningitis in Japan. PMID:15757569

  5. Cerebrospinal fluid filtration in amyotrophic lateral sclerosis.

    PubMed

    Finsterer, J; Mamoli, B

    1999-09-01

    By means of a randomized, controlled and open study the authors wanted to find out if cerebrospinal (CSF)-filtration was of substantial benefit to patients with sporadic amyotrophic lateral sclerosis (SALS). Five SALS patients, aged 51-75 years, being treated with riluzole underwent CSF-filtration daily over five days (group A). Five other SALS patients, aged 52-70 years, were treated only with riluzole (group B). Although all five patients in the first group reported a subjective benefit following CSF- filtration, the Norris score, the Frenchay score, the vital capacity, the ulnar nerve F-wave persistence and the peak-ratio of the brachial biceps and anterior tibial muscles did not change significantly after five days of therapy, either in group A or in group B. In conclusion, filtration of 200-250 ml CSF daily, over five days, does not seem to have a substantial therapeutic effect in patients with SALS. PMID:10457394

  6. Upcoming candidate cerebrospinal fluid biomarkers of Alzheimer’s disease

    PubMed Central

    Fagan, Anne M; Perrin, Richard J

    2012-01-01

    Dementia due to Alzheimer’s disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current AD clinical diagnosis, biomarkers of AD pathologies are currently being sought. Reductions in cerebrospinal fluid levels of ?-amyloid 42 (a marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are well-established as biomarkers useful for AD diagnosis and prognosis. However, novel markers for other features of AD pathophysiology (e.g., ?-amyloid processing, neuroinflammation and neuronal stress/dysfunction) and for other non-AD dementias are required to improve the accuracy of AD disease diagnosis, prognosis, staging and therapeutic monitoring (theragnosis). This article discusses the potential of several promising novel cerebrospinal fluid analytes, highlights the next steps critical for advancement in the field, and provides a prediction on how the field may evolve in 5–10 years. PMID:22917147

  7. Neurogenesis at the Brain–Cerebrospinal Fluid Interface

    PubMed Central

    Lehtinen, Maria K.; Walsh, Christopher A.

    2013-01-01

    Cerebral cortical progenitor cells can be classified into several different types, and each progenitor type integrates cell-intrinsic and cell-extrinsic cues to regulate neurogenesis. On one hand, cell-intrinsic mechanisms that depend upon appropriate apical-basal polarity are established by adherens junctions and apical complex proteins and are particularly important in progenitors with apical processes contacting the lateral ventricle. The apical protein complexes themselves are con-centrated at the ventricular surface, and apical complex proteins regulate mitotic spindle orientation and cell fate. On the other hand, remarkably little is known about how cell-extrinsic cues signal to progenitors and couple with cell-intrinsic mechanisms to instruct neurogenesis. Recent research shows that the cerebrospinal fluid, which contacts apical progenitors at the ventricular surface and bathes the apical complex of these cells, provides growth- and survival-promoting cues for neural progenitor cells in developing and adult brain. This review addresses how the apical-basal polarity of progenitor cells regulates cell fate and allows progenitors to sample diffusible signals distributed by the cere-brospinal fluid. We also review several classes of signaling factors that the cerebrospinal fluid distributes to the developing brain to instruct neurogenesis. PMID:21801012

  8. Molecular Detection of Leptospira in Two Returned Travelers: Higher Bacterial Load in Cerebrospinal Fluid Versus Serum or Plasma.

    PubMed

    Waggoner, Jesse J; Soda, Elizabeth A; Seibert, Ryan; Grant, Philip; Pinsky, Benjamin A

    2015-08-01

    Leptospirosis is a potentially severe illness in returned travelers. Patients often present with fever, headache, and neck pain, which may lead to a workup for meningitis including the acquisition of cerebrospinal fluid (CSF). Although Leptospira DNA has been detected in CSF by polymerase chain reaction (PCR), little data exist regarding the utility of testing CSF in addition to serum or plasma obtained on presentation. In this report, we present two cases of leptospirosis in returned travelers presenting with fever and headache. Our first patient had neutrophilic meningitis, and Leptospira was detectable only in CSF obtained on admission. The second patient had a normal CSF profile, but Leptospira was detected in CSF at a bacterial load 5- to 10-fold higher than that in plasma. CSF is an important specimen for the diagnosis of Leptospira by molecular methods and may yield an actionable diagnosis in the absence of leptospiremia. PMID:26033024

  9. Cerebrospinal fluid volume analysis for hydrocephalus diagnosis and clinical research.

    PubMed

    Lebret, Alain; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe; Petit, Eric

    2013-04-01

    In this paper we analyze volumes of the cerebrospinal fluid spaces for the diagnosis of hydrocephalus, which are served as reference values for future studies. We first present an automatic method to estimate those volumes from a new three-dimensional whole body magnetic resonance imaging sequence. This enables us to statistically analyze the fluid volumes, and to show that the ratio of subarachnoid volume to ventricular one is a proportionality constant for healthy adults (=10.73), while in range [0.63, 4.61] for hydrocephalus patients. This indicates that a robust distinction between pathological and healthy cases can be achieved by using this ratio as an index. PMID:23570816

  10. Development of polymerase chain reaction assays for detection of Listeria monocytogenes in clinical cerebrospinal fluid samples.

    PubMed Central

    Jaton, K; Sahli, R; Bille, J

    1992-01-01

    In order to improve the diagnosis of Listeria meningitis or meningoencephalitis, especially in patients who have received antibiotics before their cerebrospinal fluid (CSF) has been examined, two assays for the detection of Listeria monocytogenes based on the polymerase chain reaction (PCR) were evaluated. After a standard PCR, the amplified DNA was detected either by a second round of PCR with internal primers followed by gel electrophoresis and ethidium bromide staining (nested PCR) or by dot blot hybridization to an internal digoxigenin-labeled probe (PCR-dot blot). For PCR, two sets of primers within the invasion-associated protein gene (iap gene) were chosen. They allowed for the highly specific detection of all L. monocytogenes reference strains tested (serotypes 1/2a, 1/2b, 1/2c, 3a, 3b, 3c, 4a, 4b, 4c, 4d, and 7). These primers did not detect amplification products from various other gram-positive or gram-negative bacterial DNAs or human DNA. The sensitivities of both assays were assessed on sterile CSF samples that were artificially seeded with serial dilutions of L. monocytogenes serotype 4b cells. By both methods the limit of detection was less than 10 cells in the initial reaction. Since the nested PCR is more prone to contamination because of manipulation of the amplified products, a standard PCR assay followed by dot blot hybridization was applied to 52 CSF samples in a retrospective study. Of 28 CSF samples which were sterile or positive for bacteria other than Listeria species, 24 were PCR negative. In contrast, from 17 patients with culture-proven Listeria meningitis, 14 of 17 initial CSF samples were PCR positive, as were 3 of 7 culture-negative followup CSF samples taken after patients received antibiotics. These results support the usefulness of this approach in the diagnosis of Listeria meningitis, in particular, when antibiotic administration precedes culture of CSF. Images PMID:1500495

  11. Detection of Mycobacterium tuberculosis in cerebrospinal fluid following immunomagnetic enrichment.

    PubMed Central

    Mazurek, G H; Reddy, V; Murphy, D; Ansari, T

    1996-01-01

    The detection of Mycobacterium tuberculosis by culture of cerebrospinal fluid (CSF) is unacceptably slow. Low numbers of organisms and the presence of reaction inhibitors may prevent detection of M. tuberculosis by PCR. We used immunomagnetic enrichment to accelerate and enhance the detection of mycobacteria in CSF after demonstrating the utility of the method with pure suspensions. Growth was detected earlier in Bactec cultures of magnetically recovered mycobacteria than in untreated CSF (7 versus 15 days). We detected M. tuberculosis DNA by PCR in the immunomagnetically enriched sample but not in untreated CSF. PCR fingerprintings of the immunomagnetically recovered M. tuberculosis and of the isolate subsequently recovered by culture were identical. PMID:8789037

  12. Detection of Mycobacterium tuberculosis in cerebrospinal fluid following immunomagnetic enrichment.

    PubMed

    Mazurek, G H; Reddy, V; Murphy, D; Ansari, T

    1996-02-01

    The detection of Mycobacterium tuberculosis by culture of cerebrospinal fluid (CSF) is unacceptably slow. Low numbers of organisms and the presence of reaction inhibitors may prevent detection of M. tuberculosis by PCR. We used immunomagnetic enrichment to accelerate and enhance the detection of mycobacteria in CSF after demonstrating the utility of the method with pure suspensions. Growth was detected earlier in Bactec cultures of magnetically recovered mycobacteria than in untreated CSF (7 versus 15 days). We detected M. tuberculosis DNA by PCR in the immunomagnetically enriched sample but not in untreated CSF. PCR fingerprintings of the immunomagnetically recovered M. tuberculosis and of the isolate subsequently recovered by culture were identical. PMID:8789037

  13. Clinical Evaluation of a Loop-Mediated Isothermal Amplification (LAMP) Assay for Rapid Detection of Neisseria meningitidis in Cerebrospinal Fluid

    PubMed Central

    Kilgore, Paul E.; Kim, Soon Ae; Takahashi, Hideyuki; Ohnishi, Makoto; Anh, Dang Duc; Dong, Bai Qing; Kim, Jung Soo; Tomono, Jun; Miyamoto, Shigehiko; Notomi, Tsugunori; Kim, Dong Wook; Seki, Mitsuko

    2015-01-01

    Background Neisseria meningitidis (Nm) is a leading causative agent of bacterial meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed by bacterial culture. However, isolation of bacteria from patients’ cerebrospinal fluid (CSF) is time consuming and sometimes yields negative results. Recently, polymerase chain reaction (PCR)-based diagnostic methods of detecting Nm have been considered the gold standard because of their superior sensitivity and specificity compared with culture. In this study, we developed a loop-mediated isothermal amplification (LAMP) method and evaluated its ability to detect Nm in cerebrospinal fluid (CSF). Methodology/Principal Findings We developed a meningococcal LAMP assay (Nm LAMP) that targets the ctrA gene. The primer specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C, D, 29-E, W-135, X, Y, and Z) and 19 non-N. meningitidis species. Within 60 min, the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold more than that of conventional PCR. The LAMP assays were evaluated using a set of 1574 randomly selected CSF specimens from children with suspected meningitis collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were positive by LAMP vs. 25 by PCR). The detection rate of the LAMP method was substantially higher than that of the PCR method. In a comparative analysis of the PCR and LAMP assays, the clinical sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP assay were 100%, 99.6%, 80.6%, and 100%, respectively. Conclusions/Significance Compared to PCR, LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive and specific LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings. PMID:25853422

  14. Cerebrospinal fluid pressure in conscious head-down tilted rats

    NASA Technical Reports Server (NTRS)

    Severs, Walter B.; Morrow, Bret A.; Keil, Lanny C.

    1991-01-01

    The acute effects of a 1-h -45 deg head-down tilt on continouously recorded cerebrospinal fluid pressure (PCSF) of conscious rats are studied in order to investigate the shift of blood volume into the thoracic cavity in microgravity. PCSF, evaluated in 15-min time blocks over a 3-h experiment, increased slightly (less than 0.05) during the first 30 min of a control hour at 0 deg. There was a transient increase for about 5 min immediately after tilt (-45 deg) that may have been due to head movement after the position change. PCSF was statistically unchanged (above 0.05) during the second (-45 deg) hour and the third (0 deg) recovery hour. It is shown that the dynamics of intracranial pressure regulation can accommodate the acute cephalad fluid shift after tilting.

  15. Evaluation of the Production and Absorption of Cerebrospinal Fluid

    PubMed Central

    MIYAJIMA, Masakazu; ARAI, Hajime

    2015-01-01

    The traditional hypothesis of cerebrospinal fluid (CSF) hydrodynamics presumes that CSF is primarily produced in the choroid plexus (CP), then flows from the ventricles into the subarachnoid spaces, and mainly reabsorbed in the arachnoid granulations. This hypothesis is necessary to reconsider in view of recent research and clinical observations. This literature review presents numerous evidence for a new hypothesis of CSF hydrodynamics—(1) A significantly strong relationship exists between the CSF and interstitial fluid (IF), (2) CSF and IF are mainly produced and absorbed in the parenchymal capillaries of the brain and spinal cord. A considerable amount of CSF and IF are also absorbed by the lymphatic system, and (3) CSF movement is not unidirectional flow. It is only local mixing and diffusion. PMID:26226980

  16. Ganciclovir penetrates into the cerebrospinal fluid of an infant with congenital cytomegalovirus infection.

    PubMed

    Natale, Fabio; Bizzarri, Bianca; Cardi, Veronica; Gaeta, Aurelia; Villani, Paola; Liuzzi, Giuseppina; De Curtis, Mario

    2015-01-01

    Currently, there is no evidence whether ganciclovir, or its oral prodrug valganciclovir, penetrates into the cerebrospinal fluid of human infants treated for congenital cytomegalovirus infection. Here, we report a case study providing evidence that ganciclovir, administered as valganciclovir, reaches the infant's cerebrospinal fluid when used at the currently recommended dose for congenital cytomegalovirus infection. PMID:25888518

  17. Bacterial meningitis in infants.

    PubMed

    Ku, Lawrence C; Boggess, Kim A; Cohen-Wolkowiez, Michael

    2015-03-01

    Neonatal bacterial meningitis is uncommon but devastating. Morbidity among survivors remains high. The types and distribution of pathogens are related to gestational age, postnatal age, and geographic region. Confirming the diagnosis is difficult. Clinical signs are often subtle, lumbar punctures are frequently deferred, and cerebrospinal fluid (CSF) cultures can be compromised by prior antibiotic exposure. Infants with bacterial meningitis can have negative blood cultures and normal CSF parameters. Promising tests such as the polymerase chain reaction require further study. Prompt treatment with antibiotics is essential. Clinical trials investigating a vaccine for preventing neonatal Group B Streptococcus infections are ongoing. PMID:25677995

  18. Antibiotic susceptibility of type b Haemophilus influenzae and Streptococcus pneumoniae, and antibiotic concentration in cerebrospinal fluid.

    PubMed

    Fujita, K; Zhang, D H; Sakata, H; Murono, K; Kakehashi, H; Yoshioka, H

    1990-04-01

    Antibiotic susceptibilities of 38 type b Haemophilus influenzae and 28 Streptococcus pneumoniae strains isolated from cerebrospinal fluid, blood and other specimens between 1973 and 1988 were studied. Minimal inhibitory concentrations (MICs) of ampicillin against 10 beta-lactamase positive and 28 negative H. influenzae isolates were 32-64 and 0.25 micrograms/ml, respectively. The MIC of chloramphenicol against one of the beta-lactamase positive H. influenzae strains was 8 but MICs against the rest of the organisms were 0.5-1 micrograms/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all H. influenzae strains were 0.016, 0.008 and 0.5 micrograms/ml, respectively. No S. pneumoniae isolates were resistant to penicillin G and MICs of this drug were 0.016-0.032 micrograms/ml. MICs of cefotaxime, cefriaxone and cefuroxime against all S. pneumoniae strains were 0.016-0.032, 0.016-0.032 and 0.032-0.063 micrograms/ml, respectively. MICs of chloramphenicol against 15, 4 and 9 of S. pneumoniae isolates were 2, 8 and 16 micrograms/ml, respectively. Antibiotic concentrations in the cerebrospinal fluid of patients with bacterial meningitis after intravenous administration of ampicillin (50-70 mg/kg x 4/day), penicillin G (31-63 mg/kg x 4/day), cefotaxime (50 mg/kg x 4/day) and chloramphenicol (25 mg/kg x 4/day) were 4.70 +/- 1.83 (n = 11), 0.57 +/- 0.32 (n = 7), 4.97 +/- 2.60 (n = 9) and 8.52 +/- 3.54 micrograms/ml (n = 3), respectively. The initial choice of antibiotics in older children with bacterial meningitis is a combination of ampicillin (75 mg/kg x 4/day) and cefotaxime (50 mg/kg x 4/day) to cover ampicillin-resistant H. influenzae, S. pneumoniae, and Listeria monocytogenes in Japan. These antibiotics should be changed according to the causative organisms and their antibiotic susceptibilities. PMID:2116062

  19. Evaluation of Microbial Bacterial and Fungal Diversity in Cerebrospinal Fluid Shunt Infection

    PubMed Central

    Simon, Tamara D.; Pope, Christopher E.; Browd, Samuel R.; Ojemann, Jeffrey G.; Riva-Cambrin, Jay; Mayer-Hamblett, Nicole; Rosenfeld, Margaret; Zerr, Danielle M.; Hoffman, Lucas

    2014-01-01

    Background Cerebrospinal fluid shunt infection can be recalcitrant. Recurrence is common despite appropriate therapy for the pathogens identified by culture. Improved diagnostic and therapeutic approaches are required, and culture-independent molecular approaches to cerebrospinal fluid shunt infections have not been described. Objectives To identify the bacteria and fungi present in cerebrospinal fluid from children with cerebrospinal fluid shunt infection using a high-throughput sequencing approach, and to compare those results to those from negative controls and conventional culture. Methods This descriptive study included eight children ?18 years old undergoing treatment for culture-identified cerebrospinal fluid shunt infection. After routine aerobic culture of each cerebrospinal fluid sample, deoxyribonucleic acid (DNA) extraction was followed by amplification of the bacterial 16S rRNA gene and the fungal ITS DNA region tag-encoded FLX-Titanium amplicon pyrosequencing and microbial phylogenetic analysis. Results The microbiota analyses for the initial cerebrospinal fluid samples from all eight infections identified a variety of bacteria and fungi, many of which did not grow in conventional culture. Detection by conventional culture did not predict the relative abundance of an organism by pyrosequencing, but in all cases, at least one bacterial taxon was detected by both conventional culture and pyrosequencing. Individual bacterial species fluctuated in relative abundance but remained above the limits of detection during infection treatment. Conclusions Numerous bacterial and fungal organisms were detected in these cerebrospinal fluid shunt infections, even during and after treatment, indicating diverse and recalcitrant shunt microbiota. In evaluating cerebrospinal fluid shunt infection, fungal and anaerobic bacterial cultures should be considered in addition to aerobic bacterial cultures, and culture-independent approaches offer a promising alternative diagnostic approach. More effective treatment of cerebrospinal fluid shunt infections is needed to reduce unacceptably high rates of reinfection, and this work suggests that one effective strategy may be reduction of the diverse microbiota present in infection. PMID:24421877

  20. [Current cerebrospinal fluid diagnostics for pathogen-related diseases].

    PubMed

    Süssmuth, S D; Brettschneider, J; Spreer, A; Wick, M; Jesse, S; Lewerenz, J; Otto, M; Tumani, H

    2013-02-01

    Cerebrospinal fluid (CSF) analysis is of utmost importance to establish an early diagnosis of central nervous system (CNS) infections and to start appropriate therapy. The CSF white cell count, lactate concentration and total protein levels are usually available very quickly even from non-specialized laboratories and the combination of these parameters often provides sufficient information for decision-making in emergency cases. It is, however, not always possible to identify the underlying infective agent despite further CSF analyses, such as bacterial and fungal staining, evaluation of the blood-CSF barrier function, intrathecal immunoglobulin synthesis and oligoclonal IgG bands. Therefore, close communication between the laboratory and the clinician is an important prerequisite to specify additional pathogen-related diagnostic measures for successful confirmation of the diagnosis. PMID:23371378

  1. Huntington's disease cerebrospinal fluid seeds aggregation of mutant huntingtin.

    PubMed

    Tan, Z; Dai, W; van Erp, T G M; Overman, J; Demuro, A; Digman, M A; Hatami, A; Albay, R; Sontag, E M; Potkin, K T; Ling, S; Macciardi, F; Bunney, W E; Long, J D; Paulsen, J S; Ringman, J M; Parker, I; Glabe, C; Thompson, L M; Chiu, W; Potkin, S G

    2015-11-01

    Huntington's disease (HD), a progressive neurodegenerative disease, is caused by an expanded CAG triplet repeat producing a mutant huntingtin protein (mHTT) with a polyglutamine-repeat expansion. Onset of symptoms in mutant huntingtin gene-carrying individuals remains unpredictable. We report that synthetic polyglutamine oligomers and cerebrospinal fluid (CSF) from BACHD transgenic rats and from human HD subjects can seed mutant huntingtin aggregation in a cell model and its cell lysate. Our studies demonstrate that seeding requires the mutant huntingtin template and may reflect an underlying prion-like protein propagation mechanism. Light and cryo-electron microscopy show that synthetic seeds nucleate and enhance mutant huntingtin aggregation. This seeding assay distinguishes HD subjects from healthy and non-HD dementia controls without overlap (blinded samples). Ultimately, this seeding property in HD patient CSF may form the basis of a molecular biomarker assay to monitor HD and evaluate therapies that target mHTT. PMID:26100538

  2. Cerebrospinal fluid transthyretin: aging and late onset Alzheimer's disease

    PubMed Central

    Serot, J; Christmann, D; Dubost, T; Couturier, M

    1997-01-01

    The deposition of insoluble ?-amyloid protein fibrils is probably the central event in the pathogenesis of Alzheimer's disease. Cerebrospinal fluid inhibits this fibril formation, likely by the intervention of one or several proteins binding to soluble ?-amyloid protein. In vitro, transthyretin (TTR), a CSF protein, impedes amyloid fibrillogenesis. Lowered concentrations of CSFTTR could therefore be associated with Alzheimer's disease. Concentrations of TTR in CSF samples from 149 consecutive patients were assayed, using a kinetic nephelemetric method. These concentrations were correlated positively with age, but were significantly lower in patients with Alzheimer's disease. These data raise the possibility that amyloid fibril formation could be promoted in patients with late onset Alzheimer's disease by the lack of sufficient concentrations of TTR.?? PMID:9343132

  3. Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.

    PubMed

    Chiasserini, Davide; van Weering, Jan R T; Piersma, Sander R; Pham, Thang V; Malekzadeh, Arjan; Teunissen, Charlotte E; de Wit, Heidi; Jiménez, Connie R

    2014-06-25

    Extracellular vesicles (EVs) are present in human cerebrospinal fluid (CSF), yet little is known about their protein composition. The aim of this study is to provide a comprehensive analysis of the proteome of CSF EVs by electron microscopy and high resolution tandem mass spectrometry (MS/MS) in conjunction with bioinformatics. We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. Out of 1315 proteins, 760 were identified in both CSF pools and about 30% of those were also quantitatively enriched in the EV fraction versus the soluble CSF fraction. The proteome of CSF EVs was enriched in exosomal markers such as alix and syntenin-1, heat shock proteins and tetraspanins and contained a high proportion of brain-derived proteins (n=373). Interestingly, several known biomarkers for neurodegenerative diseases such as the amyloid precursor protein, the prion protein and DJ-1 were identified in the EV fractions. Our dataset represents the first comprehensive inventory of the EV proteome in CSF, underscoring the biomarker potential of this organelle. Further comparative studies on CSF EVs isolated from patients diagnosed with neurological disorders are warranted. Data are available via ProteomeXchange with identifier PXD000608. Biological significance In this study we analyzed the protein composition of extracellular vesicles isolated from pooled samples of human cerebrospinal fluid (CSF). CSF is a colorless fluid surrounding the brain and the spinal cord, important for the physiology of the central nervous system, ensuing mechanical protection, regulation of brain blood flow and elimination of byproducts of the brain. Since brain (patho)physiology is reflected in CSF, this biological fluid represents an ideal source of soluble and vesicle-based biomarkers for neurological diseases. Here we confirm the presence of exosome-like extracellular vesicles in CSF, underscoring a potential role in the physiology of the brain. These extracellular vesicles provide a rich source of candidate biomarkers, representing a brain "fluid biopsy". Most interestingly, the involvement of extracellular vesicles in transferring toxic proteins such as ?-synuclein and ?-amyloid has been postulated as one of the mechanisms involved in the spreading of neurodegeneration to different brain areas. In line with this, we show that human CSF extracellular vesicles contain prionogenic proteins such as the amyloid precursor protein and the prion protein. Delineating the protein composition of extracellular vesicles in CSF is a first and crucial step to comprehend their origin and their function in the central nervous system and to establish their biomarker potential. PMID:24769233

  4. Expression of certain proteins in the subfornical organ and cerebrospinal fluid of spontaneously hypertensive rats.

    PubMed

    González-Marrero, I; Carmona-Calero, E M; Fernández-Rodríguez, P; Pérez-González, H; Ormazabal-Ramos, C; Castañeyra-Ruiz, L; Pérez-García, C G; Martínez-Peña-Valenzuela, I; Castañeyra-Ruiz, A; Castañeyra-Perdomo, A; Ferres-Torres, R

    2007-12-01

    The objective of this study was to analyze the proteins in the cerebrospinal fluid of spontaneously hypertensive rats and to study their possible role in the relationship between hydrocephalus, arterial hypertension and variations in the subfornical organ. Brains and cerebrospinal fluid from control Wistar-Kyoto rats and spontaneously hypertensive rats sacrificed with chloral hydrate were used. Cerebrospinal fluid and extract of subfornical organ were processed by protein electrophoresis. Antisera against protein bands of 141, 117 and 48 kDa and Concanavalin A were used for immunohistochemical and western blot study of the subfornical organ, adjacent circumventricular structures and cerebrospinal fluid. Ventricular dilation in the spontaneously hypertensive rats and the presence of quite a lot of protein bands in the cerebrospinal fluid of the hypertensive rats, which were either not observed or scarcely present in the cerebrospinal fluid of the Wistar-Kyoto rats, were confirmed. The subfornical organ, third ventricle ependyma and choroideus plexus showed immunoreactive material for antibodies against 141kDa, 117 and 48 kDa proteins band (anti-B1, anti-B2 and anti-B3). The larger amount of the immunoreactive material was found in the subfornical organ of the spontaneously hypertensive rat. Our results and the alterations observed by other authors in the subfornical organ in hydrocephalic and hypertensive rats support the possibility that this circumventricular organ, some proteins of the cerebrospinal fluid and ventricular dilation could be connected with the physiopathology of this type of hypertension. PMID:17701917

  5. Embryonic blood-cerebrospinal fluid barrier formation and function

    PubMed Central

    Bueno, David; Parvas, Maryam; Hermelo, Ismaïl; Garcia-Fernàndez, Jordi

    2014-01-01

    During embryonic development and adult life, brain cavities and ventricles are filled with cerebrospinal fluid (CSF). CSF has attracted interest as an active signaling medium that regulates brain development, homeostasis and disease. CSF is a complex protein-rich fluid containing growth factors and signaling molecules that regulate multiple cell functions in the central nervous system (CNS). The composition and substance concentrations of CSF are tightly controlled. In recent years, it has been demonstrated that embryonic CSF (eCSF) has a key function as a fluid pathway for delivering diffusible signals to the developing brain, thus contributing to the proliferation, differentiation and survival of neural progenitor cells, and to the expansion and patterning of the brain. From fetal stages through to adult life, CSF is primarily produced by the choroid plexus. The development and functional activities of the choroid plexus and other blood–brain barrier (BBB) systems in adults and fetuses have been extensively analyzed. However, eCSF production and control of its homeostasis in embryos, from the closure of the anterior neuropore when the brain cavities become physiologically sealed, to the formation of the functional fetal choroid plexus, has not been studied in as much depth and remains open to debate. This review brings together the existing literature, some of which is based on experiments conducted by our research group, concerning the formation and function of a temporary embryonic blood–CSF barrier in the context of the crucial roles played by the molecules in eCSF. PMID:25389383

  6. Recent insights into a new hydrodynamics of the cerebrospinal fluid.

    PubMed

    Bulat, Marin; Klarica, Marijan

    2011-01-01

    According to the traditional hypothesis, the cerebrospinal fluid (CSF) is secreted inside the brain ventricles and flows unidirectionally along subarachnoid spaces to be absorbed into venous sinuses across arachnoid villi and/or via paraneural sheaths of nerves into lymphatics. However, according to recent investigations, it appears that interstitial fluid (ISF) and CSF are formed by water filtration across the walls of arterial capillaries in the central nervous system (CNS), while plasma osmolytes are sieved (retained) so that capillary osmotic counterpressure is generated, which is instrumental in ISF/CSF water absorption into venous capillaries and postcapillary venules. This hypothesis is supported by experiments showing that water, which constitutes 99% of CSF and ISF bulk, does not flow along CSF spaces since it is rapidly absorbed into adjacent CNS microvessels, while distribution of other substances along CSF spaces depends on the rate of their removal into microvessels: faster removal means more limited distribution. Furthermore, the acute occlusion of aqueduct of Sylvius does not change CSF pressure in isolated ventricles, suggesting that the formation and the absorption of CSF are in balance. Multidirectional distribution of substances inside CSF, as well as between CSF and ISF, is caused by to-and-fro pulsations of these fluids and their mixing. Absorption of CSF into venous sinuses and/or lymphatics under the physiological pressure should be of minor importance due to their minute surface area in comparison to the huge absorptive surface area of microvessels. PMID:20817024

  7. Penetration of trovafloxacin into cerebrospinal fluid in humans following intravenous infusion of alatrofloxacin.

    PubMed Central

    Cutler, N R; Vincent, J; Jhee, S S; Teng, R; Wardle, T; Lucas, G; Dogolo, L C; Sramek, J J

    1997-01-01

    A single-dose study was conducted to determine concentrations of trovafloxacin (CP-99,219) achieved in the cerebrospinal fluid (CSF) relative to those in the serum of healthy subjects after intravenous infusion of alatrofloxacin (CP-116,517), the alanyl-alanyl prodrug of trovafloxacin. Twelve healthy subjects were administered single doses of alatrofloxacin at a trovafloxacin equivalent of 300 mg as an intravenous infusion over 1.0 h. CSF samples were taken by lumbar puncture at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 24 h after the start of the infusion; each subject was sampled at only one time point. Serum samples were taken from each subject at the time of CSF collection. A mean concentration of 5.8 microg of trovafloxacin per ml was present in serum 1.0 h after the start of the infusion. CSF/serum ratios ranged from 0.14 to 0.33 in the postdistribution phase (5 to 24 h postinfusion), with a mean ratio of 0.25. The most common adverse events were dizziness, nausea, and rash and were mild or moderate in intensity. The potency of trovafloxacin against susceptible organisms, coupled with its rapid penetration of CSF following the intravenous administration of alatrofloxacin, suggests that it may be useful in the treatment of bacterial meningitis in humans. PMID:9174187

  8. Idiopathic cerebrospinal fluid overproduction: case-based review of the pathophysiological mechanism implied in the cerebrospinal fluid production

    PubMed Central

    Trevisi, Gianluca; Frassanito, Paolo; Di Rocco, Concezio

    2014-01-01

    Cerebrospinal fluid (CSF) overproduction results from either CSF infection or choroid plexus hypertrophy or tumor, with only a single idiopathic case described so far. We report a unique case of a male infant with Crouzon syndrome who presented with intracranial hypertension, caused by up to 4-fold increase in CSF daily production. Conditions related to CSF overproduction, namely central nervous system infections and choroid plexus hypertrophy or tumor, were ruled out by repeated magnetic resonance imaging and CSF samples. Medical therapy failed to reduce CSF production and the patient underwent several shunting procedures, cranial expansion, and endoscopic coagulation of the choroid plexus. This article thoroughly reviews pertinent literature on CSF production mechanisms and possible therapeutic implications. PMID:25165051

  9. Review of "Proteins of the Cerebrospinal Fluid" (2nd Edition) by Edward J. Thompson

    PubMed Central

    Connor, James R

    2007-01-01

    This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF.

  10. Diagnosis of lymphomatous leptomeningitis by cerebrospinal fluid lymphocyte cell surface markers.

    PubMed

    Goodson, J D; Strauss, G M

    1979-06-01

    We present a patient with metastatic lymphomatous leptomeningitis in whom the diagnosis was made on the basis of cerebrospinal fluid lymphocyte surface markers and later confirmed by cerebrospinal fluid cytology. The diagnosis of metastatic leptomeningitis can be elusive, and the differential includes a wide variety of infectious and noninfectious processes. We propose that lymphocyte surface marker studies can be a useful technique in expediting the evaluation of certain patients with lymphoma who have evidence of central nervous sytem involvement. PMID:110146

  11. Rickettsial meningitis.

    PubMed

    Salva, Inês; de Sousa, Rita; Gouveia, Catarina

    2014-01-01

    Rickettsial infections are common in southern Europe and the most frequent and lethal type is Mediterranean spotted fever, caused by Rickettsia conorii. The disease is usually characterised by the classical triad of fever, eschar and rash, and is generally a mild disease in children. Complications including neurological involvement are rarely described. We report an unusual case of meningitis in an 18-year-old man, presenting during summer with fever and persistent headache. The cerebrospinal fluid analysis revealed increased cellularity (107 cells/?L), hypoglycorrhachia (50% of glycaemia) and hyperproteinorrhachia (284 mg/dL). Rickettsial infection was confirmed by serology and the patient was treated with doxycycline, with a favourable outcome. The patient's pet squirrel and/or associated vectors might be involved in the transmission of Rickettsia spp. This case underlines the importance of a high clinical suspicion and the benefits of early empirical treatment when facing compatible epidemiological contexts. PMID:24614778

  12. Reduced cerebrospinal fluid ethanolamine concentration in major depressive disorder.

    PubMed

    Ogawa, Shintaro; Hattori, Kotaro; Sasayama, Daimei; Yokota, Yuki; Matsumura, Ryo; Matsuo, Junko; Ota, Miho; Hori, Hiroaki; Teraishi, Toshiya; Yoshida, Sumiko; Noda, Takamasa; Ohashi, Yoshiaki; Sato, Hajime; Higuchi, Teruhiko; Motohashi, Nobutaka; Kunugi, Hiroshi

    2015-01-01

    Amino acids play key roles in the function of the central nervous system, and their alterations are implicated in psychiatric disorders. In the search for a biomarker for major depressive disorder (MDD), we used high-performance liquid chromatography to measure amino acids and related molecules in the cerebrospinal fluid (CSF) of 52 patients with MDD (42 depressed and 10 remitted; DSM-IV) and 54 matched controls. Significant differences were found in four amino acid concentrations between the depressed patients and controls. After Bonferroni correction, only ethanolamine (EA) levels remained significantly reduced in depressed patients (nominal P = 0.0000011). A substantial proportion of the depressed patients (40.5%) showed abnormally low CSF EA levels (<12.1 ?M) (P = 0.000033; OR = 11.6, 95% CI: 3.1-43.2). When patients with low EA and those with high EA levels were compared, the former had higher scores for overall depression severity (P = 0.0033) and 'Somatic Anxiety' symptoms (P = 0.00026). In unmedicated subjects, CSF EA levels showed a significant positive correlation with levels of homovanillic acid (P = 0.0030) and 5-hydroxyindoleacetic acid (P = 0.019). To our knowledge, this is the first study showing that patients with MDD have significantly lower CSF EA concentrations compared with control subjects. CSF EA could be a state-dependent biomarker for a subtype of MDD. PMID:25589364

  13. The longitudinal cerebrospinal fluid metabolomic profile of amyotrophic lateral sclerosis.

    PubMed

    Gray, Elizabeth; Larkin, James R; Claridge, Tim D W; Talbot, Kevin; Sibson, Nicola R; Turner, Martin R

    2015-12-01

    Neurochemical biomarkers are urgently sought in ALS. Metabolomic analysis of cerebrospinal fluid (CSF) using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy is a highly sensitive method capable of revealing nervous system cellular pathology. The (1)H-NMR CSF metabolomic signature of ALS was sought in a longitudinal cohort. Six-monthly serial collection was performed in ALS patients across a range of clinical sub-types (n = 41) for up to two years, and in healthy controls at a single time-point (n = 14). A multivariate statistical approach, partial least squares discriminant analysis, was used to determine differences between the NMR spectra from patients and controls. Significantly predictive models were found using those patients with at least one year's interval between recruitment and the second sample. Glucose, lactate, citric acid and, unexpectedly, ethanol were the discriminating metabolites elevated in ALS. It is concluded that (1)H-NMR captured the CSF metabolomic signature associated with derangements in cellular energy utilization connected with ALS, and was most prominent in comparisons using patients with longer disease duration. The specific metabolites identified support the concept of a hypercatabolic state, possibly involving mitochondrial dysfunction specifically. Endogenous ethanol in the CSF may be an unrecognized novel marker of neuronal tissue injury in ALS. PMID:26121274

  14. Plasma and cerebrospinal fluid pharmacokinetics of flurbiprofen in children

    PubMed Central

    Kumpulainen, Elina; Välitalo, Pyry; Kokki, Merja; Lehtonen, Marko; Hooker, Andrew; Ranta, Veli-Pekka; Kokki, Hannu

    2010-01-01

    AIMS This study was designed to characterize paediatric pharmacokinetics and central nervous system exposure of flurbiprofen. METHODS The pharmacokinetics of flurbiprofen were studied in 64 healthy children aged 3 months to 13 years, undergoing surgery with spinal anaesthesia. Children were administered preoperatively a single dose of flurbiprofen intravenously as prodrug (n = 27) or by mouth as syrup (n = 37). A single cerebrospinal fluid (CSF) sample (n = 60) was collected at the induction of anaesthesia, and plasma samples (n = 304) before, during and after the operation (up to 20 h after administration). A population pharmacokinetic model was built using the NONMEM software package. RESULTS Flurbiprofen concentrations in plasma were well described by a three compartment model. The apparent bioavailability of oral flurbiprofen syrup was 81%. The estimated clearance (CL) was 0.96 l h?1 70 kg?1. Age did not affect the clearance after weight had been included as a covariate. The estimated volume of distribution at steady state (Vss) was 8.1 l 70 kg?1. Flurbiprofen permeated into the CSF, reaching concentrations that were seven-fold higher compared with unbound plasma concentrations. CONCLUSIONS Flurbiprofen pharmacokinetics can be described using only weight as a covariate in children above 6 months, while more research is needed in neonates and in younger infants. PMID:20840447

  15. Cerebrospinal Fluid Biomarkers in Spinocerebellar Ataxia: A Pilot Study

    PubMed Central

    Brouillette, Ashley M.; Öz, Gülin; Gomez, Christopher M.

    2015-01-01

    Neurodegenerative diseases, including the spinocerebellar ataxias (SCA), would benefit from the identification of reliable biomarkers that could serve as disease subtype-specific and stage-specific indicators for the development and monitoring of treatments. We analyzed the cerebrospinal fluid (CSF) level of tau, ?-synuclein, DJ-1, and glial fibrillary acidic protein (GFAP), proteins previously associated with neurodegenerative processes, in patients with the autosomal dominant SCA1, SCA2, and SCA6, and the sporadic disease multiple system atrophy, cerebellar type (MSA-C), compared with age-matched controls. We estimated disease severity using the Scale for the Assessment and Rating of Ataxia (SARA). Most proteins measured trended higher in disease versus control group yet did not reach statistical significance. We found the levels of tau in both SCA2 and MSA-C patients were significantly higher than control. We found that ?-synuclein levels were lower with higher SARA scores in SCA1 and tau levels were higher with greater SARA in MSA-C, although this final correlation did not reach statistical significance after post hoc correction. Additional studies with larger sample sizes are needed to improve the power of these studies and validate the use of CSF biomarkers in SCA and MSA-C. PMID:26265793

  16. Increased cerebrospinal fluid fibrinogen in major depressive disorder

    PubMed Central

    Hattori, Kotaro; Ota, Miho; Sasayama, Daimei; Yoshida, Sumiko; Matsumura, Ryo; Miyakawa, Tomoko; Yokota, Yuuki; Yamaguchi, Shinobu; Noda, Takamasa; Teraishi, Toshiya; Hori, Hiroaki; Higuchi, Teruhiko; Kohsaka, Shinichi; Goto, Yu-ichi; Kunugi, Hiroshi

    2015-01-01

    Major depressive disorder (MDD) presumably includes heterogeneous subgroups with differing pathologies. To obtain a marker reflecting such a subgroup, we analyzed the cerebrospinal fluid (CSF) levels of fibrinogen, which has been reported to be elevated in the plasma of patients with MDD. Three fibrinogen-related proteins were measured using aptamer-based analyses and CSF samples of 30 patients with MDD and 30 controls. The numbers of patients with an excessively high level (>99 percentile of the controls) was significantly increased (17 to 23%). Measurement reproducibility of these results was confirmed by an ELISA for fibrinogen (Pearson’s r?=?0.77). In an independent sample set from 36 patients and 30 controls, using the ELISA, results were similar (22%). When these two sample sets were combined, the number of patients with a high fibrinogen level was significantly increased (15/66; odds ratio 8.53; 95% confidence interval 1.9–39.1, p?=?0.0011). By using diffusion tensor imaging, we found white matter tracts abnormalities in patients with a high fibrinogen level but not those patients with a normal fibrinogen level, compared with controls. Plasma fibrinogen levels were similar among the diagnostic groups. Our results point to a subgroup of MDD represented by increased CSF fibrinogen and white matter tract abnormalities. PMID:26081315

  17. Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid

    PubMed Central

    He, Ping; Kramer, Kim; Smith-Jones, Peter; Zanzonico, Pat; Humm, John; Larson, Steven M.

    2011-01-01

    Purpose Radioimmunotherapy (RIT) using 131I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of 131I-3F8 and to identify limiting factors that may impact therapeutic ratio. Methods Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[CIAR]), (2) that of the unbound antibody AUC[CIA], and (3) their therapeutic ratio (AUC [CIAR]/AUC[CIA]). Results Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R=0.95±0.03). Correlations were substantially better when compared to the one-compartment model (R=0.92±0.11 versus 0.77±0.21, p=0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of 131I-3F8 from 10% to 90% increased both (AUC[CIAR]) and therapeutic ratio ([AUC[CIAR]/AUC[CIA

  18. Nasoseptal Flap Closure of Traumatic Cerebrospinal Fluid Leaks

    PubMed Central

    Wheless, Stephan A.; McKinney, Kibwei A.; Carrau, Ricardo L.; Snyderman, Carl H.; Kassam, Amin B.; Germanwala, Anand V.; Zanation, Adam M.

    2010-01-01

    The vascularized nasoseptal flap has become a principal reconstructive technique for the closure of endonasal skull base surgery defects. Despite its potential utility, there has been no report describing the use of the modern nasoseptal flap to repair traumatic cerebrospinal fluid (CSF) leaks and documenting the outcomes of this application. Specific concerns in skull base trauma include septal trauma with disruption of the flap pedicle, multiple leak sites, and issues surrounding persistent leaks after traumatic craniotomy. We performed a retrospective case series review of 14 patients who underwent nasoseptal flap closure of traumatic CSF leaks in a tertiary academic hospital. Main outcome measures include analysis of clinical outcome data. Defect etiology was motor vehicle collision in eight patients (57%), prior sinus surgery in four (29%), and assault in two (14%). At the time of nasoseptal flap repair, four patients had failed prior avascular grafts and two had previously undergone craniotomies for repair. Follow-up data were available for all patients (mean, 10 months). The overall success rate was 100% (no leaks), with 100% defect coverage. The nasoseptal flap is a versatile and reliable local reconstructive technique for ventral base traumatic defects, with a 100% CSF leak repair rate in this series. PMID:22451808

  19. Short-term stability of Borrelia garinii in cerebrospinal fluid.

    PubMed

    Berenová, Dagmar; Krsek, Daniel; Šípková, Lenka; Lukavská, Alena; Malý, Marek; Kurzová, Zuzana; Ho?ejší, Jan; Kodym, Petr

    2016-01-01

    The aim of our study was to find out the optimal conditions for short-term storage of cerebrospinal fluid (CSF) samples for direct diagnosis of Lyme disease. A mixture of Borrelia-negative CSFs spiked with a defined amount of cultured Borrelia garinii was used. Borrelia stability was investigated over 7 days at four different temperatures [room temperature (RT), +4, -20 and -70 °C]. Quantitative changes in CSF Borrelia were measured by quantitative PCR (qPCR), and morphological changes in the spirochetes were observed by transmission electron microscopy (TEM). These qPCR results were statistically evaluated. We found +4 °C to be an optimal temperature for short-term storage of CSF samples intended for TEM observation. There was no significant difference between the temperatures tested in the average quantity of Borrelia measured by qPCR. On the contrary, electron optical diagnosis of frozen samples and samples stored at RT showed destructive morphological changes and decreased spirochete counts. Our results show that optimal conditions for the pre-analytical phase of investigation of one type of material can differ depending on the diagnostic method employed. PMID:26104540

  20. Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.

    PubMed

    Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj

    2015-11-01

    Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (? = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. PMID:26373605

  1. Analysis of cerebrospinal fluid and cerebrospinal fluid cells from patients with multiple sclerosis for detection of JC virus DNA

    PubMed Central

    lacobaeus, E; Ryschkewitsch, C; Gravell, M; Khademi, M; Wallstrom, E; Olsson, T; Brundin, L; Major, EO

    2009-01-01

    Objective 1) To determine whether JC virus (JCV) DNA was present in the cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) in comparison with controls and 2) to find out if our clinical material, based on presence of JCV DNA, included any patient at risk for progressive multifocal leukoencephalopathy (PML). Methods The prevalence of JCV DNA was analyzed in CSF and plasma from 217 patients with MS, 86 patients with clinically isolated syndrome (CIS), and 212 patients with other neurological diseases (OND). In addition, we analyzed CSF cells, the first report of JCV DNA in CSF cells in a single sample, and peripheral blood cells in a subgroup of MS (n = 49), CIS (n = 14) and OND (n = 53). Results A low copy number of JCV DNA was detected in one MS cell free CSF sample and in one MS CSF cell samples. None of these had any signs of PML or developed this disease during follow-up. In addition, two OND plasma samples were JCV DNA positive, whereas all the other samples had no detectable virus. Conclusion A low copy number of JCV DNA may occasionally be observed both in MS and other diseases and may occur as part of the normal biology of JC virus in humans. This study does not support the hypothesis that patients with MS would be at increased risk to develop PML, and consequently screening of CSF as a measurable risk for PML is not useful. PMID:18805840

  2. Cerebrospinal fluid physiology: visualization of cerebrospinal fluid dynamics using the magnetic resonance imaging Time-Spatial Inversion Pulse method

    PubMed Central

    Yamada, Shinya

    2014-01-01

    Previously there have been no methods for directly tracing the flow of cerebrospinal fluid (CSF) under physiological conditions, and the circulation of CSF has therefore been studied and visualized by injecting a radioactively labeled tracer or contrast medium visible in x-ray images. The newly developed Time-Spatial Inversion Pulse (Time-SLIP) method makes it possible to directly visualize the flow of CSF using magnetic resonance imaging (MRI), permitting CSF dynamics to be depicted in a certain time frame. The CSF dynamics visualized using Time-SLIP has been found to differ markedly from the classical CSF circulation theory described in medical textbooks. It can be said that research on CSF dynamics has advanced to the next stage with the use of this innovative imaging method. Obtaining a more accurate understanding of normal CSF physiology and pathophysiology should lead to improved diagnostic accuracy, permit the identification of new etiological factors in a variety of diseases, and promote the development of new therapeutic approaches. PMID:25165048

  3. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines.

    PubMed

    Warrington, Junie P

    2015-11-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ~13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R(2) = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  4. Cerebrospinal Fluid A? to Tau Ratio and Postoperative Cognitive Change

    PubMed Central

    Xie, Zhongcong; McAuliffe, Sayre; Swain, Celeste A.; Ward, Sarah A. P.; Crosby, Catherine A.; Zheng, Hui; Sherman, Janet; Dong, Yuanlin; Zhang, Yiying; Sunder, Neelakantan; Burke, Dennis; Washicosky, Kevin J.; Tanzi, Rudolph E.; Marcantonio, Edward R.

    2013-01-01

    Objective Determination of biomarker and neuropathogenesis of postoperative cognitive change (POCC) or postoperative cognitive dysfunction. Background POCC is one of the most common postoperative complications in elderly patients. Whether preoperative cerebrospinal fluid (CSF) ?-amyloid protein (A?) to tau ratio, an Alzheimer disease biomarker, is a biomarker for risk of POCC remains unknown. We therefore set out to assess the association between preoperative CSF A?42 or A?40 to tau ratio and POCC. Methods Patients who had total hip/knee replacement were enrolled. The CSF was obtained during the administration of spinal anesthesia. Cognitive tests were performed with these participants at 1 week before and at 1 week and 3 to 6 months after the surgery. Z scores of the changes from preoperative to postoperative on several key domains of the cognitive battery were determined. We then examined the association between preoperative CSF A?42/tau or A?40/tau ratio and the outcome measures described earlier, adjusting for age and sex. Results Among the 136 participants (mean age = 71 ± 5 years; 55% men), preoperative CSF A?42/tau ratio was associated with postoperative Hopkins Verbal Learning Test Retention [Z score 8.351; age, sex-adjusted (adj.) P = 0.003], and the Benton Judgment of Line= Orientation (Z score 1.242; adj. p = 0.007). A?40/tau ratio was associated with Brief Visuospatial Memory Test Total Recall (Z score = 1.045; adj. P = 0.044). Conclusions Preoperative CSF A?/tau ratio is associated with postoperative changes in specific cognitive domains. The presence of the Alzheimer's disease biomarker, specifically the A?/tau ratio, may identify patients at higher risk for cognitive changes after surgery. PMID:23732272

  5. Preoperative cerebrospinal fluid ?-Amyloid/Tau ratio and postoperative delirium

    PubMed Central

    Xie, Zhongcong; Swain, Celeste A; Ward, Sarah A P; Zheng, Hui; Dong, Yuanlin; Sunder, Neelakantan; Burke, Dennis W; Escobar, Diana; Zhang, Yiying; Marcantonio, Edward R

    2014-01-01

    Objective The neuropathogenesis of postoperative delirium remains unknown. Low cerebrospinal fluid (CSF) ?-amyloid protein (A?) and high CSF Tau levels are associated with Alzheimer's disease. We, therefore, assessed whether lower preoperative CSF A?/Tau ratio was associated with higher incidence and greater severity of postoperative delirium. Methods One hundred and fifty-three participants (71 ± 5 years, 53% men) who had total hip/knee replacement under spinal anesthesia were enrolled. CSF was obtained during initiation of spinal anesthesia. The incidence and severity of postoperative delirium were determined by Confusion Assessment Method (CAM) and Memorial Delirium Assessment Scale (MDAS) on postoperative day 1 and 2. A?40, A?42, and Tau levels in the CSF were measured by enzyme-linked immunosorbent assay. The relationships among these variables were determined, adjusting for age and gender. Results Participants in the lowest quartile of preoperative CSF A?40/Tau and A?42/Tau ratio had higher incidence (32% vs. 17%, P = 0.0482) and greater symptom severity of postoperative delirium (A?40/Tau ratio: 4 vs. 3, P = 0.034; A?42/Tau ratio: 4 vs. 3, P = 0.062, the median of the highest MDAS score) as compared to the combination of the rest of the quartiles. The preoperative CSF A?40/Tau or A?42/Tau ratio was inversely associated with MDAS score (A?40/Tau ratio: ?0.12 ± 0.05, P = 0.014, adj. ?0.12 ± 0.05, P = 0.018; A?42/Tau ratio: ?0.65 ± 0.26, P = 0.013, adj. ?0.62 ± 0.27, P = 0.022). Interpretation Lower CSF A?/Tau ratio could be associated with postoperative delirium, pending confirmation of our preliminary results in further studies. These findings suggest potential roles of A? and/or Tau in postoperative delirium neuropathogenesis. PMID:24860840

  6. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection

    PubMed Central

    2009-01-01

    Background Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. Methods In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPP? and sAPP?), amyloid beta fragment 1-42 (A?1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. Results CSF sAPP? and sAPP? concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF A?1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Conclusions Parallel reductions of CSF sAPP? and sAPP? in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease. PMID:20028512

  7. Placental ischemia increases seizure susceptibility and cerebrospinal fluid cytokines

    PubMed Central

    Warrington, Junie P

    2015-01-01

    Eclampsia is diagnosed in preeclamptic patients who develop unexplained seizures and/or coma during pregnancy or postpartum. Eclampsia is one of the leading causes of maternal and infant morbidity and mortality, accounting for ?13% of maternal deaths worldwide. Little is known about the mechanisms contributing to the pathophysiology of eclampsia, partly due to the lack of suitable animal models. This study tested the hypothesis that placental ischemia, induced by reducing utero-placental perfusion, increases susceptibility to seizures, cerebrospinal fluid (CSF) inflammation, and neurokinin B (NKB) expression in brain and plasma. Pentylenetetrazol (PTZ), a pro-convulsive drug, was injected into pregnant and placental ischemic rats (40 mg/kg, i.p.) on gestational day 19 followed by video monitoring for 30 min. Seizure scoring was blindly conducted. Placental ischemia hastened the onset of seizures compared to pregnant controls but had no effect on seizure duration. Placental ischemia increased CSF levels of IL-2, IL-17, IL-18 and eotaxin (CCL11), had no effect on plasma NKB; however, PTZ increased plasma NKB in both pregnant and placental ischemic rats. NKB was strongly correlated with latency to seizure in normal pregnant rats (R2 = 0.88 vs. 0.02 in placental ischemic rats). Lastly, NKB decreased in the anterior cerebrum in response to placental ischemia and PTZ treatment but was unchanged in the posterior cerebrum. These data demonstrate that placental ischemia is associated with increased susceptibility to seizures and CSF inflammation; thus provides an excellent model for elucidating mechanisms of eclampsia-like symptoms. Further studies are required to determine the role of CSF cytokines/chemokines in mediating increased seizure susceptibility. PMID:26603461

  8. Brain Gene Expression Signatures From Cerebrospinal Fluid Exosome RNA Profiling

    NASA Technical Reports Server (NTRS)

    Zanello, S. B.; Stevens, B.; Calvillo, E.; Tang, R.; Gutierrez Flores, B.; Hu, L.; Skog, J.; Bershad, E.

    2016-01-01

    While the Visual Impairment and Intracranial Pressure (VIIP) syndrome observations have focused on ocular symptoms, spaceflight has been also associated with a number of other performance and neurologic signs, such as headaches, cognitive changes, vertigo, nausea, sleep/circadian disruption and mood alterations, which, albeit likely multifactorial, can also result from elevation of intracranial pressure (ICP). We therefore hypothesize that these various symptoms are caused by disturbances in the neurophysiology of the brain structures and are correlated with molecular markers in the cerebrospinal fluid (CSF) as indicators of neurophysiological changes. Exosomes are 30-200 nm microvesicles shed into all biofluids, including blood, urine, and CSF, carrying a highly rich source of intact protein and RNA cargo. Exosomes have been identified in human CSF, and their proteome and RNA pool is a potential new reservoir for biomarker discovery in neurological disorders. The purpose of this study is to investigate changes in brain gene expression via exosome analysis in patients suffering from ICP elevation of varied severity (idiopathic intracranial hypertension -IIH), a condition which shares some of the neuroophthalmological features of VIIP, as a first step toward obtaining evidence suggesting that cognitive function and ICP levels can be correlated with biomarkers in the CSF. Our preliminary work, reported last year, validated the exosomal technology applicable to CSF analysis and demonstrated that it was possible to obtain gene expression evidence of inflammation processes in traumatic brain injury patients. We are now recruiting patients with suspected IIH requiring lumbar puncture at Baylor College of Medicine. Both CSF (5 ml) and human plasma (10 ml) are being collected in order to compare the pattern of differentially expressed genes observed in CSF and in blood. Since blood is much more accessible than CSF, we would like to determine whether plasma biomarkers for elevated ICP can be identified. This may eventually lead to a blood test to diagnose intracranial hypertension.

  9. [Recurrent episodic unilateral mydriasis with pleocytosis in the cerebrospinal fluid--a case report].

    PubMed

    Takeda, K; Sakuta, M; Takano, T

    1989-09-01

    A 24-year-old female was admitted to our hospital on Aug. 20 in 1986 because of blurred vision and right pupillary dilatation. She had sometimes noticed headache later than 1976, and blurred vision without headache several times a year later than 1983. She had been told her right pupil dilated when she had complained of blurred vision. Neurological examination revealed abnormal findings as follows; diminished sense of smell in the right side, anisocoria (R 8 mm, L 5 mm), bilateral hippus, hypesthesioalgesia in her right face, left trunk and left arm. The pupils were round and contracted promptly to light. Accommodation reflex and ciliospinal reflexes were normal. Neither blepharoptosis nor external ocular muscle paresis were observed. Deep tendon reflexes were normal. Planter responses were flexor. There was no meningeal irritative sign. No abnormal findings were obtained in blood and urine, chest X-p, brain enhanced CT scan, EEG, and cerebral angiography except for slight degree of anemia. Serum TPHA was negative. However, the cell count of cerebrospinal fluid (CSF) was 18/mm3 (Ly 100%) and decreased to 9/mm3 (Ly 100%) in nine days. Protein content and glucose level of CSF were normal. Pupils were not constricted by 0.125% pilocarpine instillation. Loss of smell and sensory disturbance disappeared within three days and her pupils became isocoric by five days after admission. The patients of episodic unilateral mydriasis without apparent cause had relatively same clinical features as "unilateral springing pupil" proposed by Hallett et al. (1970). Except for mydriasis, they had no abnormal findings of neurological and laboratory examinations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2598548

  10. Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

    PubMed

    Luykx, J J; Bakker, S C; Visser, W F; Verhoeven-Duif, N; Buizer-Voskamp, J E; den Heijer, J M; Boks, M P M; Sul, J H; Eskin, E; Ori, A P; Cantor, R M; Vorstman, J; Strengman, E; DeYoung, J; Kappen, T H; Pariama, E; van Dongen, E P A; Borgdorff, P; Bruins, P; de Koning, T J; Kahn, R S; Ophoff, R A

    2015-12-01

    The N-methyl-d-aspartate receptor (NMDAR) coagonists glycine, d-serine and l-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with l-proline in plasma (?=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with l-proline in CSF (?=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the d-serine plasma-CSF ratio at the d-amino-acid oxidase (DAO) gene (?=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the l-serine to d-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects. PMID:25666758

  11. Journal of Biomechanics 40 (2007) 12351245 Computational investigation of subject-specific cerebrospinal fluid

    E-print Network

    Daraio, Chiara

    2007-01-01

    -specific cerebrospinal fluid flow in the third ventricle and aqueduct of Sylvius Vartan Kurtcuoglua,Ã, Michaela ventricle of the brain and the aqueduct of Sylvius was studied using computational fluid dynamics (CFD to reconstruct the velocity field at the inferior end of the aqueduct of Sylvius based on the theory of pulsatile

  12. [Cytologic examination of the cerebrospinal fluid in the diagnosis of primary or metastatic neoplasms of the nervous system].

    PubMed

    De Moraes-Rêgo, S F; De Moraes-Rêgo, K G

    1986-06-01

    The authors report 6 cases of cerebrospinal fluid (CSF) examinations in which malignant cells were found. In 5 cases the finding was incidental: medulloblastoma (case 1); malignant melanoma (case 2); adenocarcinoma (case 3); meningitis carcinomatosa (case 4) and neuroleukaemia (case 5). In only one case neuroleukaemia was suspected before the study of the CSF (case 6). The unexpected occurrence of malignant cells in the CSF demands the pathologist to be well acquainted with tumor cell cytology, in order to identify them providing so useful information that can decidedly influence subsequent diagnostic and therapeutic procedures. The cell collection technic developed in the authors' laboratory was considered adequate, because both inflammatory and malignant cells were securely identified. Its principle is to obtain thin air-dried smears that dry almost instantaneously on slides, in order the cellular structure be preserved. After centrifuging about 5-8 ml of CSF the tube is inverted so as to pour off the whole of the supernatant fluid. It is kept inverted with the operator's left hand, so that no drop of fluid can run back on to the cells. With his right hand the operator touches the bottom of the inverted tube with a Pasteur micropipette preciously made by distending a microhematocrit tube under the flame of a Bunsen burner and attached with adhesive tape to the handle of a wire loop 2 mm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3800690

  13. [Alpha-Synuclein in blood and cerebrospinal fluid of patients with alpha-synucleinopathy].

    PubMed

    Ono, Kenjiro; Yamada, Masahito

    2014-03-01

    Alpha-Synuclein protein(alphaS) aggregates from a monomer to assemblies such as oligomers, protofibrils, and mature fibrils. The early intermediate aggregate, that is, the oligomer, has been reported to be the most toxic species. We recently reported that melatonin inhibits alphaS aggregation, including protofibril and oligomer formations. While the alphaS concentration in cerebrospinal fluid was reported to significantly decrease in patients with Parkinson's disease (PD) and dementia with Lewy bodies, there have been reports that the alphaS oligomer concentration was elevated in the cerebrospinal fluid of PD patients. Moreover, it was reported that the alphaS oligomer concentration was also elevated in the blood of PD patients. Further studies may establish alphaS in cerebrospinal fluid and blood as a biomarker of alpha-synucleinopathies, including PD. PMID:24800499

  14. Meningeal leishmaniosis induced by Leishmania infantum in naturally infected dogs.

    PubMed

    Viñuelas, J; García-Alonso, M; Ferrando, L; Navarrete, I; Molano, I; Mirón, C; Carcelén, J; Alonso, C; Nieto, C G

    2001-10-31

    We report two cases of meningitis caused by Leishmania infantum in naturally infected dogs. In both of these dogs the typical phenotypic features of granulomatous meningitis were observed with important lympho-plasma-cellular infiltrates and the presence of large numbers of parasites inside and outside macrophages. The immunological study of the cerebrospinal fluid of both animals showed that a large number of protein bands were recognized by those fluids and that they were similar to the ones recognized by the sera from the same animals. To our knowledge, this is the first description of meningitis associated to leishmaniosis. PMID:11587830

  15. Analysis of cerebrospinal fluid in racemose form of neurocysticercosis.

    PubMed

    Bazan, Rodrigo; Odashima, Newton Satoru; Luvizutto, Gustavo José; Hamamoto Filho, Pedro Tadao; Zanini, Marco Antonio; Takayanagui, Osvaldo Massaiti

    2015-10-01

    The present work aimed to evaluate the pattern of CSF alterations in patients diagnosed with neurocysticercosis (NCC) in racemose form.Method This is a retrospective cohort study of patients with diagnosis of NCC in racemose form. CSF samples from 26 patients were analyzed. After patient-chart analysis was performed descriptive analysis of case studies and comparison between sexes in relation to variables were obtained with CSF by Mann-Whitney and Student's t-tests.Results The sexes did not differ statistically when compared to pleocytosis in CSF. Eosinophils were present in 31% in samples while the ELISA test presented 80% sensitivity in this case series. Of the patient total, 24 presented a meningitis pattern with lymphocytic predominance.Conclusion There was no difference in inflammatory pattern between the sexes, with predominance of lymphocytic meningitis and 80% sensitivity by ELISA test of CSF patients with racemose form of NCC. PMID:26291994

  16. Clinically severe Epstein-Barr virus encephalitis with mild cerebrospinal fluid abnormalities in an immunocompetent adolescent: a case report.

    PubMed

    Engelmann, Ilka; Nasser, Hala; Belmiloudi, Soufien; Le Guern, Rémi; Dewilde, Anny; Vallée, Louis; Hober, Didier

    2013-06-01

    A 15-year-old boy developed Epstein-Barr virus (EBV) encephalitis, a rare complication of infectious mononucleosis. The severe clinical picture and the marked neuroimaging changes were in contrast with mild cerebrospinal fluid abnormalities: leukocyte count was normal and protein level was only slightly elevated. EBV DNA was detected in cerebrospinal fluid by polymerase chain reaction. PMID:23535207

  17. Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

    PubMed

    Sadarangani, Manish; Willis, Louise; Kadambari, Seilesh; Gormley, Stuart; Young, Zoe; Beckley, Rebecca; Gantlett, Katherine; Orf, Katharine; Blakey, Sarah; Martin, Natalie G; Kelly, Dominic F; Heath, Paul T; Nadel, Simon; Pollard, Andrew J

    2015-03-01

    Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16?years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3?months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3?months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay. PMID:25256088

  18. Pathogenesis and pathophysiology of bacterial meningitis.

    PubMed Central

    Tunkel, A R; Scheld, W M

    1993-01-01

    Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder. Images PMID:8472245

  19. Bacterial meningitis: new therapeutic approaches.

    PubMed

    Nau, Roland; Djukic, Marija; Spreer, Annette; Eiffert, Helmut

    2013-10-01

    Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden. PMID:24073921

  20. Progressive Differentiation and Instructive Capacities of Amniotic Fluid and Cerebrospinal Fluid Proteomes following Neural Tube Closure.

    PubMed

    Chau, Kevin F; Springel, Mark W; Broadbelt, Kevin G; Park, Hye-Yeon; Topal, Salih; Lun, Melody P; Mullan, Hillary; Maynard, Thomas; Steen, Hanno; LaMantia, Anthony S; Lehtinen, Maria K

    2015-12-21

    After neural tube closure, amniotic fluid (AF) captured inside the neural tube forms the nascent cerebrospinal fluid (CSF). Neuroepithelial stem cells contact CSF-filled ventricles, proliferate, and differentiate to form the mammalian brain, while neurogenic placodes, which generate cranial sensory neurons, remain in contact with the AF. Using in vivo ultrasound imaging, we quantified the expansion of the embryonic ventricular-CSF space from its inception. We developed tools to obtain pure AF and nascent CSF, before and after neural tube closure, and to define how the AF and CSF proteomes diverge during mouse development. Using embryonic neural explants, we demonstrate that age-matched fluids promote Sox2-positive neurogenic identity in developing forebrain and olfactory epithelia. Nascent CSF also stimulates SOX2-positive self-renewal of forebrain progenitor cells, some of which is attributable to LIFR signaling. Our Resource should facilitate the investigation of fluid-tissue interactions during this highly vulnerable stage of early brain development. PMID:26702835

  1. Letter to the editor: Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent report (Formisano et al., 2013) identified clinical sacrocystosis in 2 adult sheep. The diagnosis relied primarily on characterization of DNA extracted from cerebrospinal fluid (CSF) and paraffin-embedded heart tissue. Parasites identified as merozoites were identified in CSF smears stained...

  2. Acute Cerebral Phaeohyphomycosis due to Wangiella dermatitidis Accompanied by Cerebrospinal Fluid Eosinophilia

    PubMed Central

    Chang, Chulhun Ludgerus; Kim, Dae-Seong; Park, Dong June; Kim, Hak Jin; Lee, Chang Hun; Shin, Jong Hee

    2000-01-01

    We report a case of cerebral phaeohyphomycosis due to Wangiella dermaitidis in an immunocompetent adult man. His cerebrospinal fluid (CSF) showed pleocytosis with a high eosinophil count but without peripheral blood eosinophilia. The present case suggested that this black yeast-like fungus should be included when the causes of CSF eosinophilia are considered, even though it is an extremely rare pathogen. PMID:10790129

  3. Genome Sequence of Acinetobacter baumannii Strain 5021_13, Isolated from Cerebrospinal Fluid

    PubMed Central

    Kumar, Sunil; Patil, Prashant P.; Midha, Samriti; Ray, Pallab

    2015-01-01

    We report here the 4.1-Mb draft genome sequence of Acinetobacter baumannii strain 5021_13, a cerebrospinal fluid isolate from northern India. This genome information will help studies toward understanding the epidemiology and pathogenicity of this important nosocomial pathogen. PMID:26472849

  4. Extensive Recruitment of Plasma Blasts to the Cerebrospinal Fluid in Toscana Virus Encephalitis.

    PubMed

    Schirmer, Lucas; Wölfel, Silke; Georgi, Enrico; Ploner, Markus; Bauer, Barbara; Hemmer, Bernhard

    2015-09-01

    An unexpectedly extensive recruitment of B cells and plasma blasts to the cerebrospinal fluid (CSF) in a patient with Toscana virus (TOSV) encephalitis is described. Acute infection by TOSV was demonstrated by serological methods and by detection of TOSV-specific nucleic acid in the CSF by real-time polymerase chain reaction and sequencing. PMID:26393235

  5. Extensive Recruitment of Plasma Blasts to the Cerebrospinal Fluid in Toscana Virus Encephalitis

    PubMed Central

    Schirmer, Lucas; Wölfel, Silke; Georgi, Enrico; Ploner, Markus; Bauer, Barbara; Hemmer, Bernhard

    2015-01-01

    An unexpectedly extensive recruitment of B cells and plasma blasts to the cerebrospinal fluid (CSF) in a patient with Toscana virus (TOSV) encephalitis is described. Acute infection by TOSV was demonstrated by serological methods and by detection of TOSV-specific nucleic acid in the CSF by real-time polymerase chain reaction and sequencing. PMID:26393235

  6. Seizures and retrograde amnesia with cerebrospinal fluid changes following H1N1 influenza vaccination.

    PubMed

    Mitrakrishnan, Shivanthan; Ranjanie, Gamage; Thirunavakarasu, Thivakaran; Manjula, Caldera; Nayananjani, Karunasena

    2011-08-26

    Vaccination against H1N1 influenza of healthcare workers of has been a standard measure to control the epidemic in many countries. Most side effects are minor and transient. Guillain Barre Syndrome and optic neuritis have been major concerns. We report a case of seizures with retrograde amnesia associated with cerebrospinal fluid changes following the H1N1 vaccine. PMID:21840464

  7. [Group A streptococcal meningitis: Streptococcus pneumoniae is not the only one to seep into the CSF fluid leak!].

    PubMed

    Zappella, N; Barrelet, A; Pangon, B; Laurent, V; Bruneel, F

    2013-11-01

    We reported a case of group A streptococcal meningitis in a patient with a CSF fluid leak. This case underlined several relevant points: (i) an unfrequent cause of bacterial meningitis; (ii) the main diagnosis to evoke when the direct examination of CSF shows Gram+ cocci with a negative pneumococcal antigen; (iii) that bacteria other than Streptococcus pneumoniae are possible in front of a meningitis associated with a CSF fluif leak. PMID:24161291

  8. Infantile Salmonella meningitis associated with gecko-keeping.

    PubMed

    Cyriac, J; Wozniak, E R

    2000-03-01

    A serotype found mainly in reptiles was isolated from cerebrospinal fluid from a 2 month old baby with meningitis. A related salmonella was isolated from gecko faeces from the floor of the tank in the baby's home, suggesting a possible source of infection, and indicating the need for hygienic precautions in homes where reptiles are kept as pets. PMID:10743325

  9. Cerebrospinal Fluid from Patients with Subarachnoid Haemorrhage and Vasospasm Enhances Endothelin Contraction in Rat Cerebral Arteries

    PubMed Central

    Assenzio, Barbara; Martin, Erica L.; Stankevicius, Edgaras; Civiletti, Federica; Fontanella, Marco; Boccaletti, Riccardo; Berardino, Maurizio; Mazzeo, AnnaTeresa; Ducati, Alessandro; Simonsen, Ulf; Mascia, Luciana

    2015-01-01

    Introduction Previous studies have suggested that cerebrospinal fluid from patients with subarachnoid hemorrhage (SAH) leads to pronounced vasoconstriction in isolated arteries. We hypothesized that only cerebrospinal fluid from SAH patients with vasospasm would produce an enhanced contractile response to endothelin-1 in rat cerebral arteries, involving both endothelin ETA and ETB receptors. Methods Intact rat basilar arteries were incubated for 24 hours with cerebrospinal fluid from 1) SAH patients with vasospasm, 2) SAH patients without vasospasm, and 3) control patients. Arterial segments with and without endothelium were mounted in myographs and concentration-response curves for endothelin-1 were constructed in the absence and presence of selective and combined ETA and ETB receptor antagonists. Endothelin concentrations in culture medium and receptor expression were measured. Results Compared to the other groups, the following was observed in arteries exposed to cerebrospinal fluid from patients with vasospasm: 1) larger contractions at lower endothelin concentrations (p<0.05); 2) the increased endothelin contraction was absent in arteries without endothelium; 3) higher levels of endothelin secretion in the culture medium (p<0.05); 4) there was expression of ETA receptors and new expression of ETB receptors was apparent; 5) reduction in the enhanced response to endothelin after ETB blockade in the low range and after ETA blockade in the high range of endothelin concentrations; 6) after combined ETA and ETB blockade a complete inhibition of endothelin contraction was observed. Conclusions Our experimental findings showed that in intact rat basilar arteries exposed to cerebrospinal fluid from patients with vasospasm endothelin contraction was enhanced in an endothelium-dependent manner and was blocked by combined ETA and ETB receptor antagonism. Therefore we suggest that combined blockade of both receptors may play a role in counteracting vasospasm in patients with SAH. PMID:25629621

  10. Immunoglobulin G avidity testing in serum and cerebrospinal fluid for analysis of measles virus infection.

    PubMed Central

    Narita, M; Yamada, S; Matsuzono, Y; Itakura, O; Togashi, T; Kikuta, H

    1996-01-01

    We studied a variety of patients with measles virus infection by using avidity testing for measles virus-specific immunoglobulin G (IgG) in serum and cerebrospinal fluid samples. For the avidity testing, an Enzygnost measles IgG enzyme-linked immunosorbent assay kit was used with an 8 M urea denaturing method. With this method, low-avidity IgG (acute primary infection, avidity of < 30% within 15 days of the onset of rash) and high-avidity IgG (subacute sclerosing panencephalitis, avidity of > 75%) could be clearly distinguished by using serum samples. One patient, who developed a typical course of measles despite a previous vaccination, showed a positive IgM response with an initial low titer of measles virus-specific IgG of low avidity, but a later sample revealed a high titer of IgG of intermediate (40%) avidity, suggesting previous immunological priming. Two patients with breakthrough infection (secondary vaccine failure), both having central nervous system involvement, showed a positive IgM response with initial high titers of serum IgG of high avidity. In addition, one of the patients had a detectable level of measles-specific IgG in cerebrospinal fluid. In this patient, the avidity of both serum and cerebrospinal fluid IgG decreased during the short follow-up period. This phenomenon has never before been reported. In subacute sclerosing panencephalitis patients, the avidity of cerebrospinal fluid IgG was consistently lower than that of serum IgG. The difference in avidity between cerebrospinal fluid and serum IgG may be used as a direct indicator of intrathecal production of IgG. In conclusion, the avidity testing is simple to perform, reliable, and highly informative in the analysis of measles virus infection. PMID:8991638

  11. Echographic correlation of optic nerve sheath size and cerebrospinal fluid pressure.

    PubMed

    Galetta, S; Byrne, S F; Smith, J L

    1989-06-01

    A 23-year-old obese woman presented with papilledema. Computed tomography showed no intracranial mass lesions and lumbar puncture revealed an increased opening pressure, confirming the diagnosis of pseudo-tumor cerebri. Standardized echography of the optic nerves was performed immediately before and after lumbar puncture. A marked reduction of cerebrospinal fluid pressure correlated with a decrease in the subarachnoid fluid of the optic nerve sheath. PMID:2526162

  12. A Practical Approach to Meningitis and Encephalitis.

    PubMed

    Richie, Megan B; Josephson, S Andrew

    2015-12-01

    Meningitis is an inflammatory syndrome involving the meninges that classically manifests with headache and nuchal rigidity and is diagnosed by cerebrospinal fluid examination. In contrast, encephalitis refers to inflammation of the brain parenchyma itself and often results in focal neurologic deficits or seizures. In this article, the authors review the differential diagnosis of meningitis and encephalitis, with an emphasis on infectious etiologies. The recommended practical clinical approach focuses on early high-yield diagnostic testing and empiric antimicrobial administration, given the high morbidity associated with these diseases and the time-sensitive nature of treatment initiation. If the initial workup does not yield a diagnosis, further etiology-specific testing based upon risk factors and clinical characteristics should be pursued. Effective treatment is available for many causes of meningitis and encephalitis, and when possible should address both the primary disease process as well as potential complications. PMID:26595861

  13. FDG PET in Intracranial Carcinomatous Meningitis.

    PubMed

    Heimburger, Céline; Bund, Caroline; Namer, Izzie Jacques

    2016-01-01

    A 63-year-old white man, diagnosed with pT3N2 squamous cell lung carcinoma, underwent right upper lobectomy with adjuvant radiochemotherapy. After a partial epileptic seizure, MRI revealed a solitary right frontal metastasis that was treated with surgical resection followed by stereotaxic radiotherapy. Three months later, the patient presented weight loss, weakness, and headache. He underwent a whole-body FDG PET/CT for restaging. It showed intense FDG uptakes on the brain periphery corresponding to nodular meningeal contrast enhancement on MRI leading to the diagnosis of carcinomatous meningitis, despite negative cerebrospinal fluid cytology. PMID:26447391

  14. A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases*

    PubMed Central

    Menon, Krishnakumar N.; Steer, David L.; Short, Martin; Petratos, Steven; Smith, Ian; Bernard, Claude C. A.

    2011-01-01

    Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as ?? crystallin, enolase, and 14–3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin response mediator protein-2 was increased, whereas Ubiquitin carboxy-terminal hydrolase L1 was down-regulated, not only highlights the importance of these molecules in the pathology of this disease, but also illustrates the use of our approach in attempting to decipher the complex pathological processes leading to multiple sclerosis and other neurodegenerative diseases. PMID:21421798

  15. Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression

    PubMed Central

    Southwell, Amber L.; Smith, Stephen E.P.; Davis, Tessa R.; Caron, Nicholas S.; Villanueva, Erika B.; Xie, Yuanyun; Collins, Jennifer A.; Li Ye, Min; Sturrock, Aaron; Leavitt, Blair R.; Schrum, Adam G.; Hayden, Michael R.

    2015-01-01

    Quantitation of huntingtin protein in the brain is needed, both as a marker of Huntington disease (HD) progression and for use in clinical gene silencing trials. Measurement of huntingtin in cerebrospinal fluid could be a biomarker of brain huntingtin, but traditional protein quantitation methods have failed to detect huntingtin in cerebrospinal fluid. Using micro-bead based immunoprecipitation and flow cytometry (IP-FCM), we have developed a highly sensitive mutant huntingtin detection assay. The sensitivity of huntingtin IP-FCM enables accurate detection of mutant huntingtin protein in the cerebrospinal fluid of HD patients and model mice, demonstrating that mutant huntingtin levels in cerebrospinal fluid reflect brain levels, increasing with disease stage and decreasing following brain huntingtin suppression. This technique has potential applications as a research tool and as a clinical biomarker. PMID:26174131

  16. Increased cerebrospinal fluid interleukin-8 in bipolar disorder patients associated with lithium and antipsychotic treatment.

    PubMed

    Isgren, Anniella; Jakobsson, Joel; Pålsson, Erik; Ekman, Carl Johan; Johansson, Anette G M; Sellgren, Carl; Blennow, Kaj; Zetterberg, Henrik; Landén, Mikael

    2015-01-01

    Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication. PMID:25451615

  17. Prevalence and implications of cerebrospinal fluid leukocytosis in Papua New Guinean children hospitalized with severe malaria.

    PubMed

    Laman, Moses; Manning, Laurens; Siba, Peter M; Davis, Timothy M E

    2013-11-01

    Cerebrospinal fluid (CSF) leukocytosis in severe malaria was assessed in 87 children in Papua New Guinea participating in a detailed longitudinal observational study who had undergone lumbar puncture for further investigation of altered consciousness and/or convulsions. After rigorous exclusion of non-malarial infection, 16 (20.5%) of 78 children with Plasmodium falciparum monoinfection but 0 of 9 with P. vivax/mixed-species malaria had a detectable CSF leukocytosis, which was unrelated to prior, including complex, seizures. There were eight children with a CSF leukocyte density > 10 cells/?L (9.2% of the total sample), half of whom had cerebral malaria (4 of 22, 18.1%). Cerebrospinal fluid leukocytosis is infrequent in severe pediatric malaria, especially in children with P. vivax infections, and it is generally mild. Its presence in a blood slide-positive child should prompt consideration of alternative diagnoses and empiric antibiotic therapy. PMID:24019433

  18. Prevalence and Implications of Cerebrospinal Fluid Leukocytosis in Papua New Guinean Children Hospitalized with Severe Malaria

    PubMed Central

    Laman, Moses; Manning, Laurens; Siba, Peter M.; Davis, Timothy M. E.

    2013-01-01

    Cerebrospinal fluid (CSF) leukocytosis in severe malaria was assessed in 87 children in Papua New Guinea participating in a detailed longitudinal observational study who had undergone lumbar puncture for further investigation of altered consciousness and/or convulsions. After rigorous exclusion of non-malarial infection, 16 (20.5%) of 78 children with Plasmodium falciparum monoinfection but 0 of 9 with P. vivax/mixed-species malaria had a detectable CSF leukocytosis, which was unrelated to prior, including complex, seizures. There were eight children with a CSF leukocyte density > 10 cells/?L (9.2% of the total sample), half of whom had cerebral malaria (4 of 22, 18.1%). Cerebrospinal fluid leukocytosis is infrequent in severe pediatric malaria, especially in children with P. vivax infections, and it is generally mild. Its presence in a blood slide–positive child should prompt consideration of alternative diagnoses and empiric antibiotic therapy. PMID:24019433

  19. Cerebrospinal fluid enolase isoenzymes and neurotoxicity in early treatment of lymphoblastic leukaemia.

    PubMed Central

    Royds, J A; Lilleyman, J S; Timperley, W R; Taylor, C B

    1984-01-01

    Serial measurements of enolase in the cerebrospinal fluid were made in 19 children with lymphoblastic leukaemia undergoing their first 6 weeks of antineoplastic treatment. The neurone-specific gamma enolase value rose appreciably in nearly all patients during the first two weeks of treatment, which comprised chemotherapy only, but the mean values for this isoenzyme failed to show any further rise during the subsequent cranial irradiation. In contrast the alpha enolase value, which is derived predominantly from glial tissue, rose progressively to attain its highest value during radiotherapy. A consideration of the likely rate of clearance of gamma enolase from the cerebrospinal fluid and the time sequence of administration of the several chemotherapeutic agents in UKALL VIII suggests that asparaginase may be the main causative agent in the rise of this marker of neuronal damage. PMID:6585185

  20. Value of cerebrospinal fluid ?-synuclein species as biomarker in Parkinson's diagnosis and prognosis.

    PubMed

    Parnetti, Lucilla; Cicognola, Claudia; Eusebi, Paolo; Chiasserini, Davide

    2016-01-01

    Since diagnosis of Parkinson's disease (PD) is mostly based on clinical criteria, it is almost impossible to formulate an early diagnosis, as well as a timely differential diagnosis versus other parkinsonisms. A great effort in searching reliable biomarkers both for early diagnosis and prognosis in PD is currently ongoing. Cerebrospinal fluid has been widely investigated as potential source for such biomarkers, with particular emphasis on ?-synuclein (?-syn) species. We reviewed all the clinical studies carried out so far on cerebrospinal fluid quantification of ?-syn species in PD. Current evidence supports the value of total and oligomeric ?-syn in PD diagnosis and in the differential diagnosis of PD and other parkinsonisms. Conversely, the role of ?-syn species in PD prognosis remains unsatisfactory. PMID:26643452

  1. Spontaneous Cerebrospinal Fluid Otorrhea from a Persistent Tympanomeningeal Fissure Presenting as Recurrent Serous Otitis Media

    PubMed Central

    Zakaryan, Arman; Poulsgaard, Lars; Hollander, Camilla; Fugleholm, Kåre

    2015-01-01

    We describe spontaneous cerebrospinal fluid (CSF) otorrhea through a patent tympanomeningeal (Hyrtl) fissure presenting as recurrent serous otitis media. The CSF leak was observed when a drain was placed through the tympanic membrane by an otologist. The diagnosis was then confirmed by computed tomography and magnetic resonance imaging, and the patient underwent a successful surgical treatment via a retrosigmoid approach. We describe the case and review causes of spontaneous CSF rhinorrhea/otorrhea. PMID:26251786

  2. Salmonella enterica Serotype Arizonae Meningitis in a Neonate.

    PubMed

    Lakew, Wubishet; Girma, Abayneh; Triche, Elizabeth

    2013-01-01

    Typhoidal and nontyphoidal salmonella infections are common causes of gastroenteritis in the community. However, salmonella only rarely causes invasive infections like meningitis. We report a 13-day-old female neonate with signs and symptoms of meningitis whose cerebrospinal fluid (CSF) culture showed Salmonella enterica serotype Arizonae that was sensitive to ceftriaxone. She presented with fever and failure to feed for 2 days. Despite prompt treatment with ampicillin, gentamicin, and ceftriaxone, she developed communicating hydrocephalus, frequent seizures, and coma that progressed to death after 2 weeks of hospitalization. Salmonella enterica serotype Arizonae is a rare cause of human infection known to leading to meningitis symptoms similar to those caused by other salmonella species. This is the first report of it as a cause of meningitis in a child under one month of age. Therefore, it should be included in the differential diagnosis of Gram-negative bacillary meningitis in immunocompromised children, neonates, and those with contacts with reptiles. PMID:24187642

  3. Salmonella enterica Serotype Arizonae Meningitis in a Neonate

    PubMed Central

    Lakew, Wubishet; Girma, Abayneh; Triche, Elizabeth

    2013-01-01

    Typhoidal and nontyphoidal salmonella infections are common causes of gastroenteritis in the community. However, salmonella only rarely causes invasive infections like meningitis. We report a 13-day-old female neonate with signs and symptoms of meningitis whose cerebrospinal fluid (CSF) culture showed Salmonella enterica serotype Arizonae that was sensitive to ceftriaxone. She presented with fever and failure to feed for 2 days. Despite prompt treatment with ampicillin, gentamicin, and ceftriaxone, she developed communicating hydrocephalus, frequent seizures, and coma that progressed to death after 2 weeks of hospitalization. Salmonella enterica serotype Arizonae is a rare cause of human infection known to leading to meningitis symptoms similar to those caused by other salmonella species. This is the first report of it as a cause of meningitis in a child under one month of age. Therefore, it should be included in the differential diagnosis of Gram-negative bacillary meningitis in immunocompromised children, neonates, and those with contacts with reptiles. PMID:24187642

  4. Postsurgical Pantoea calida meningitis: a case report

    PubMed Central

    2014-01-01

    Introduction Pantoea calida, a recently described environmental Enterobacteriaceae organism, has not yet been associated with human infection. Case presentation We report a case of postoperative meningitis caused by P. calida. After pituitary adenoma resection, a 52-year-old Caucasian woman developed febrile meningitis confirmed by cerebrospinal fluid analysis. P. calida was grown in pure culture from this fluid and was firmly identified with partial rpoB gene sequencing. She was cured by a 14-day course of meropenem. Conclusions P. calida must be added to the list of opportunistic Enterobacteriaceae pathogens responsible for postsurgical meningitis. It is easily identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. PMID:24934580

  5. Increased cerebrospinal fluid osteopontin levels and its involvement in macrophage infiltration in neuromyelitis optica

    PubMed Central

    Kariya, Yoshinobu; Kariya, Yukiko; Saito, Toshie; Nishiyama, Shuhei; Honda, Takashi; Tanaka, Keiko; Yoshida, Mari; Fujihara, Kazuo; Hashimoto, Yasuhiro

    2015-01-01

    Background Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system that predominantly affects the optic nerves and spinal cord. Although NMO has long been considered a subtype of multiple sclerosis (MS), the effects of interferon-? treatment are different between NMO and MS. Recent findings of NMO-IgG suggest that NMO could be a distinct disease rather than a subtype of MS. However, the underlying molecular mechanism of NMO pathology remains poorly understood. Methods OPN in the cerebrospinal fluid and brain of patients with NMO and with MS, as well as of patients with other neurologic disease/idiopathic other neurologic disease was examined using Western blotting, ELISA, immunohistochemistry and Boyden chamber. Results Here we show that osteopontin is significantly increased in the cerebrospinal fluid of NMO patients compared with MS patients. Immunohistochemical analyses revealed that osteopontin was markedly elevated in the cerebral white matter of NMO patients and produced by astrocytes, neurons, and oligodendroglia as well as infiltrating macrophages. We also demonstrate that the interaction of the cerebrospinal fluid osteopontin in NMO patients with integrin ?v?3 promoted macrophage chemotaxis by activating phosphoinositide 3-kinase and MEK1/2 signaling pathways. Conclusion These results indicate that osteopontin is involved in NMO pathology. General significance Thus therapeutic strategies that target osteopontin signaling may be useful to treat NMO. PMID:26673877

  6. Laboratory diagnosis of bacterial meningitis.

    PubMed Central

    Gray, L D; Fedorko, D P

    1992-01-01

    Bacterial meningitis is relatively common, can progress rapidly, and can result in death or permanent debilitation. This infection justifiably elicits strong emotional reactions and, hopefully, immediate medical intervention. This review is a brief presentation of the pathogenesis of bacterial meningitis and a review of current knowledge, literature, and recommendations on the subject of laboratory diagnosis of bacterial meningitis. Those who work in clinical microbiology laboratories should be familiar with the tests used in detecting bacteria and bacterial antigens in cerebrospinal fluid (CSF) and should always have the utmost appreciation for the fact that results of such tests must always be reported immediately. Academic and practical aspects of the laboratory diagnosis of bacterial meningitis presented in this review include the following: anatomy of the meninges; pathogenesis; changes in the composition of CSF; etiological agents; processing CSF; microscopic examination of CSF; culturing CSF; methods of detecting bacterial antigens and bacterial components in CSF (counter-immunoelectrophoresis, coagglutination, latex agglutination, enzyme-linked immunosorbent assay, Limulus amebocyte lysate assay, and gas-liquid chromatography); use of the polymerase chain reaction; and practical considerations for testing CSF for bacterial antigens. PMID:1576585

  7. Acute purulent meningitis associated with chronic subdural hematoma and subdural hygroma.

    PubMed

    Imataka, George; Miyamoto, Kenji; Fujiyama, Youko; Mitsui, Masahiko; Yoshida, Atsushi; Yamanouchi, Hideo; Arisaka, Osamu

    2007-01-01

    A male infant aged nine months with meningeal irritation and +3.5SD expansion of the circumference of the head was admitted. Brain computed tomography (CT) detected right chronic subdural hematoma and contralateral subdural hygroma. Since the cell count was increased on a cerebrospinal fluid test, acute purulent meningitis was diagnosed. A rapid latex test and culture of cerebrospinal fluid identified Streptococcus pneumoniae (PSSP) as the pathogen. Panipenem/betamiprom (PAPM/BP) was administered at 100 mg/kg/3 times for 14 days and dexamethasone was administered at 0.6 mg/kg/4 times for 4 days, and the patient recovered without sequelae. Acute purulent meningitis complicated by chronic subdural hematoma and subdural hygroma is rare. In this case, acute subdural hygroma may have concomitantly developed with acute purulent meningitis in the presence of the chronic subdural hematoma, and rapid disequilibrium of intracranial pressure may have been the developmental mechanism. PMID:18246750

  8. Development of a theoretical framework for analyzing cerebrospinal fluid dynamics

    PubMed Central

    Cohen, Benjamin; Voorhees, Abram; Vedel, Søren; Wei, Timothy

    2009-01-01

    Background To date hydrocephalus researchers acknowledge the need for rigorous but utilitarian fluid mechanics understanding and methodologies in studying normal and hydrocephalic intracranial dynamics. Pressure volume models and electric circuit analogs introduced pressure into volume conservation; but control volume analysis enforces independent conditions on pressure and volume. Previously, utilization of clinical measurements has been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Methods Control volume analysis is presented to introduce the reader to the theoretical background of this foundational fluid mechanics technique for application to general control volumes. This approach is able to directly incorporate the diverse measurements obtained by clinicians to better elucidate intracranial dynamics and progression to disorder. Results Several examples of meaningful intracranial control volumes and the particular measurement sets needed for the analysis are discussed. Conclusion Control volume analysis provides a framework to guide the type and location of measurements and also a way to interpret the resulting data within a fundamental fluid physics analysis. PMID:19772652

  9. Application of Control Volume Analysis to Cerebrospinal Fluid Dynamics

    NASA Astrophysics Data System (ADS)

    Wei, Timothy; Cohen, Benjamin; Anor, Tomer; Madsen, Joseph

    2011-11-01

    Hydrocephalus is among the most common birth defects and may not be prevented nor cured. Afflicted individuals face serious issues, which at present are too complicated and not well enough understood to treat via systematic therapies. This talk outlines the framework and application of a control volume methodology to clinical Phase Contrast MRI data. Specifically, integral control volume analysis utilizes a fundamental, fluid dynamics methodology to quantify intracranial dynamics within a precise, direct, and physically meaningful framework. A chronically shunted, hydrocephalic patient in need of a revision procedure was used as an in vivo case study. Magnetic resonance velocity measurements within the patient's aqueduct were obtained in four biomedical state and were analyzed using the methods presented in this dissertation. Pressure force estimates were obtained, showing distinct differences in amplitude, phase, and waveform shape for different intracranial states within the same individual. Thoughts on the physiological and diagnostic research and development implications/opportunities will be presented.

  10. Isoelectric focusing in agarose gel for detection of oligoclonal bands in cerebrospinal and other biological fluids.

    PubMed

    Csako, Gyorgy

    2012-01-01

    Isoelectric focusing (IEF) coupled with immunodetection (immunofixation or immunoblotting) has become the leading technique for the detection and study of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) and also is increasingly used in other body fluids such as the tear and serum. Limited commercial availability of precast agarose IEF gels for research and a need for customization prompted reporting a detailed general protocol for the preparation and casting of agarose IEF gel along with sample, control, and isoelectric point marker preparation and carrying out the focusing itself for CSF OCBs. However, the method is readily adaptable to the use of other body fluid specimens and, possibly, research specimens such as culture fluids as well. PMID:22585491

  11. Determination of nitrite and nitrate in cerebrospinal fluid by microchip electrophoresis with microsolid phase extraction pre-treatment.

    PubMed

    Troška, Peter; Chudoba, Richard; Dan?, Ladislav; Bodor, Róbert; Hor?i?iak, Michal; Tesa?ová, Eva; Masár, Marián

    2013-07-01

    A new method for the determination of nitrite and nitrate, indicators of various neurological diseases (meningitis, multiple sclerosis, Parkinson's disease) in cerebrospinal fluid (CSF) on an electrophoresis chip was developed. An on-line combination of isotachophoresis (ITP) with capillary electrophoresis (CE) on a poly(methylmethacrylate) chip assembled with coupled separation channels (CC) and contact conductivity detectors was employed. ITP separations performed at low pH (3.6) in the first separation channel enabled a highly selective transfer of the analytes to the second CE stage working under micellar conditions implemented by zwitterionic surfactant, 3-(N,N-dimethyldodecylammonio)-propanesulfonate. The proposed method achieved low limits of detection varied from 0.2 to 0.4?gL(-1) when the sample volume injected onto the chip (9.9?l) was almost the same as the volume of both separation channels. Preferable working conditions on the CC chip (suppressed hydrodynamic and electroosmotic flow) contributed for reproducible migration velocities (intra-day reproducibility up to 2.1% RSD) and determinations of trace concentrations of nitrite and nitrate (intra-day precision up to 3.0% RSD). Huge amount of chloride present in CSF (approx. 4.5gL(-1)) was removed from analyzed CSF samples by microsolid phase extraction performed on silver-form resin prior to the ITP-CE analysis. Developed method provided fast (approx. 20min total analysis time) and reliable determinations of trace nitrite and nitrate and could be fully integrated into the analysis of CSF samples. PMID:23727865

  12. A management algorithm for cerebrospinal fluid leak associated with anterior skull base fractures: detailed clinical and radiological follow-up.

    PubMed

    Sherif, Camillo; Di Ieva, Antonio; Gibson, Daniel; Pakrah-Bodingbauer, Bita; Widhalm, Georg; Krusche-Mandl, Irena; Erdoes, Jozsef; Gilloon, Benjamin; Matula, Christian

    2012-04-01

    Detailed outcome data for the management of anterior skull base fractures associated with cerebrospinal fluid (CSF) leakage is lacking. We present detailed follow-up data of a single-center study using a predetermined algorithm for the management of CSF leakage secondary to traumatic fractures. A number of 138 consecutive patients were included in the analysis; all patients underwent high-resolution computed tomography (CT) scanning at time of admission with ?(2)-transferrin testing used to confirm CSF leakage. Patients with acute surgical indications were operated as emergent; leaks were repaired at the time of initial surgery in patients with intracranial pressure?meningitis rate was low (1.9%). Postoperative CSF leak (1.9%) was managed by intradural or transnasal endoscopic operation. Comparable rates of anosmia and frontal lobe hypodensities were seen in the surgical and conservatively managed subgroups. The presented algorithm, utilizing prophylactic antibiotics, trial of LD, acute and/or delayed intradural microsurgery, yields favorable outcomes. Large randomized controlled trials are needed to better define the role of prophylactic antibiotics and to better characterize the optimal timing and approach of surgical repair. PMID:21947554

  13. Safety of intra-cerebrospinal fluid chemotherapy in onco-haematological patients: a retrospective analysis of 627 interventions.

    PubMed

    Pardo-Moreno, Javier; Fernández, Cristina; Arroyo, Rafael; Ruiz-Ocaña, Carlos; Aláez, Concepción; Cuadrado, María-Luz

    2015-11-01

    Intra-cerebrospinal fluid chemotherapy (ICC) is used widely to treat or prevent neoplastic meningitis (NM), although its safety has not been thoroughly assessed. We aimed to analyse the incidence, severity and cause of the adverse reactions provoked by ICC in a cohort of onco-haematological patients. We retrospectively reviewed all the adverse reactions related to ICC procedures performed by the same researcher over a 5-year period. We classified them according to their severity and cause, and examined their association with certain characteristics of the patients and interventions. A total of 627 procedures were performed on 124 patients, in which 59 adverse reactions were documented (9.4 %). Thirty-two (54 %) of these were considered severe and 30 (51 %) were due to the drug itself. NM was associated with a higher incidence of adverse reactions (p = 0.002) and severe adverse reactions (p < 0.001). Adverse reactions were more common (p = 0.028) and more often severe (p = 0.008) when an Ommaya reservoir was used, as opposed to the lumbar puncture procedure. The use of liposomal cytarabine was also associated with a higher incidence of adverse reactions (p < 0.001) and serious adverse reactions (p < 0.001) than immediate-release drugs. Liposomal cytarabine provoked more adverse reactions attributable to the drug when administered by lumbar puncture (p = 0.192), whereas the remaining drugs had higher risk when administered via Ommaya reservoir (p = 0.015). ICC seems a relatively safe procedure. Adverse reactions appear to be more frequent when NM is already present. Lumbar puncture seems to be safer than the Ommaya reservoir, except when liposomal cytarabine is administered. PMID:26342710

  14. Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 13 cases with mumps meningitis.

    PubMed

    Takeshima, Shinichi; Yoshimoto, Takeshi; Shiga, Yuji; Kanaya, Yuhei; Neshige, Shuichiro; Himeno, Takahiro; Kono, Ryuhei; Takamatsu, Kazuhiro; Shimoe, Yutaka; Kuriyama, Masaru

    2015-09-11

    We experienced 13 cases (29.8 ± 7.0 years) of mumps meningitis and 365 cases of adult aseptic meningitis during 11 years from 2004 to 2014. A small epidemic of mumps occurred for 3-4 years, and the incidence rate of adult mumps meningitis coincided with the epidemic without seasonal fluctuation. Parotitis was observed in 8 of the 13 mumps meningitis patients (61.5%) and orchitis in 2 of 7 male patients (28.6%). There were no differences in clinical manifestations, laboratory findings, and outcome between patients with adult mumps meningitis and those with echovirus 9 meningitis (9 patients), except for the low frequency of nausea/vomiting and a high percentage of mononuclear cells of the cerebrospinal fluid in those with mumps. Eight patients had contact with persons with mumps before the symptomatic stage of meningitis. Only one patient had received mumps vaccination in childhood. On the basis of the values of the anti-mumps IgM and IgG antibodies, we speculated primary infection and the re-infection of mumps in 6 and 2 patients, respectively. Moreover, second vaccine failure was suggested in the vaccinated patient. PMID:26156258

  15. Evaluation and Treatment of Chronic Meningitis

    PubMed Central

    Zunt, Joseph R.

    2014-01-01

    Chronic meningitis is defined as an inflammatory cerebrospinal fluid (CSF) profile that persists for at least 1 month. The presentation often includes headache, nausea, vomiting, cranial neuropathies, symptoms of elevated intracranial pressure, or focal neurologic deficits. The most common etiologies of chronic meningitis fall into 3 broad categories: infectious, autoimmune, and neoplastic. Evaluation of the patient with suspected chronic meningitis should include a detailed history and physical examination as well as repeated CSF diagnostics, serologic studies, and biopsy of the brain or other abnormal tissue (eg, lymph node or lung), when indicated. Early identification of the etiology and rapid treatment are crucial for improving morbidity and mortality, but potential infectious and neoplastic conditions should be excluded prior to empirically starting steroids or immunosuppressive medications. PMID:25360204

  16. Altered Concentrations of Amyloid Precursor Protein Metabolites in the Cerebrospinal Fluid of Patients with Bipolar Disorder

    PubMed Central

    Jakobsson, Joel; Zetterberg, Henrik; Blennow, Kaj; Johan Ekman, Carl; Johansson, Anette G M; Landén, Mikael

    2013-01-01

    Bipolar disorder is a psychiatric disorder characterized by recurrent episodes of mania/hypomania and depression. Progressive cognitive dysfunction such as impairments in executive function and verbal memory is common in euthymic bipolar patients. The cerebrospinal fluid has previously been used to study neurodegenerative processes in Alzheimer's disease, from which changes in three core biomarkers have emerged as indicative of degeneration: amyloid ?, total tau, and hyperphosphorylated tau. Here, neurodegeneration in bipolar disorder was investigated by assessing the association between bipolar disorder and cerebrospinal fluid biomarkers for neurodegenerative processes. Cerebrospinal fluid was obtained from 139 bipolar disorder patients and 71 healthy controls. Concentrations of total and phosphorylated tau, amyloid ?1-42, amyloid ?38/?40/?42, and the soluble forms of amyloid precursor protein were measured in patients vs controls. The concentrations of the soluble forms of amyloid precursor protein were significantly lower in bipolar patients compared with controls. The amyloid ?42/amyloid ?38 and the amyloid ?42/amyloid ?40 ratios were higher in bipolar patients than controls. There were no discernible differences in the concentrations of total/phosphorylated tau, amyloid ?1-42, or amyloid ?38/?40/?42. The concentrations of the biomarkers within the bipolar patient group were further associated with different ongoing medical treatments and diagnostic subgroups. The findings suggest that the amyloid precursor protein metabolism is altered in bipolar disorder. The results may have implications for the understanding of the pathophysiology of bipolar disorder and for the development of treatment strategies. Importantly, there were no signs of an Alzheimer-like neurodegenerative process among bipolar patients. PMID:23212456

  17. Cerebrospinal Fluid Hypernatremia Elevates Sympathetic Nerve Activity and Blood Pressure via the Rostral Ventrolateral Medulla.

    PubMed

    Stocker, Sean D; Lang, Susan M; Simmonds, Sarah S; Wenner, Megan M; Farquhar, William B

    2015-12-01

    Elevated NaCl concentrations of the cerebrospinal fluid increase sympathetic nerve activity (SNA) in salt-sensitive hypertension. Neurons of the rostral ventrolateral medulla (RVLM) play a pivotal role in the regulation of SNA and receive mono- or polysynaptic inputs from several hypothalamic structures responsive to hypernatremia. Therefore, the present study investigated the contribution of RVLM neurons to the SNA and pressor response to cerebrospinal fluid hypernatremia. Lateral ventricle infusion of 0.15 mol/L, 0.6 mol/L, and 1.0 mol/L NaCl (5 µL/10 minutes) produced concentration-dependent increases in lumbar SNA, adrenal SNA, and arterial blood pressure, despite no change in splanchnic SNA and a decrease in renal SNA. Ganglionic blockade with chlorisondamine or acute lesion of the lamina terminalis blocked or significantly attenuated these responses, respectively. RVLM microinjection of the gamma-aminobutyric acid (GABAA) agonist muscimol abolished the sympathoexcitatory response to intracerebroventricular infusion of 1 mol/L NaCl. Furthermore, blockade of ionotropic glutamate, but not angiotensin II type 1, receptors significantly attenuated the increase in lumbar SNA, adrenal SNA, and arterial blood pressure. Finally, single-unit recordings of spinally projecting RVLM neurons revealed 3 distinct populations based on discharge responses to intracerebroventricular infusion of 1 mol/L NaCl: type I excited (46%; 11/24), type II inhibited (37%; 9/24), and type III no change (17%; 4/24). All neurons with slow conduction velocities were type I cells. Collectively, these findings suggest that acute increases in cerebrospinal fluid NaCl concentrations selectively activate a discrete population of RVLM neurons through glutamate receptor activation to increase SNA and arterial blood pressure. PMID:26416846

  18. Gastrin and cholecystokinin in human cerebrospinal fluid. Immunochemical determination of concentrations and molecular heterogeneity.

    PubMed

    Rehfeld, J F; Kruse-Larsen, C

    1978-10-20

    To determine whether gastrin and cholecystokinin (CCK), recently found in the central nervous sytem, were present in cerebrospinal fluid (CSF), we studied human specimens by sensitive and specific radioimmunoassays for the two related polypeptide hormones. The concentration of gastrin in cerebrospinal fluid from 10 neurologically normal persons ranged from 1.5 to 8.0 pM (mean 3.4 pM), whereas the concentration of CCK ranged from 4 to 55 pM (mean 14 pM). The molecular heterogeneity of gastrin and CCK in CSF was determined by gel chromatography of concentrated fluid monitored by 3 gastrin radioimmunoassays specific for different sequences of gastrin17 and 3 CCK radioimmunoassays specific for different sequences of CCK33. Chromatography revealed that gastrin was present in molecular forms corresponding to gastrin34 ('big gastrin') and gastrin17. CCK was present in molecular forms corresponding to the COOH-terminal octapeptide amide of CCK33 and a fragment corresponding to sequence 25-29 of CCK33. Also, a peptide corresponding to COOH-terminal tetrapeptide amide common to both gastrin and CCK was found. The results indicate that true gastrin as well as CCK are present in CSF, and that both hormones display a molecular heterogeneity similar to that found in extracts of brain tissue. PMID:688012

  19. Non Invasive Microwave Sensor for the Detection of Lactic Acid in Cerebrospinal Fluid (CSF)

    NASA Astrophysics Data System (ADS)

    Goh, J. H.; Mason, A.; Al-Shamma'a, A. I.; Field, M.; Shackcloth, M.; Browning, P.

    2011-08-01

    This research involves the use of a low power microwave sensor for analysis of lactic acid in cerebrospinal fluid (CSF), an indicator of neurological impairment during aortic aneurysm surgery which could provide the basis for improved treatment regimes and better quality of care with more efficient use of resources. This paper presents initial work using standard lactate curves in water followed by lactate in "synthetic CSF". A multi-modal spectral signature has been defined for lactate, forming the basis for subsequent development of microwave sensor platform that is able to detect concentrations of lactic acid in CSF of volumes less than 1ml.

  20. State of the art of endoscopic frontal sinus cerebrospinal fluid leak repair.

    PubMed

    Patron, V; Roger, V; Moreau, S; Babin, E; Hitier, M

    2015-12-01

    Frontal sinus cerebrospinal fluid leaks are rare and their surgical management is difficult. Up until recently, they could only be treated by open surgery with an osteoplastic flap. With the development of endoscopic surgery, less invasive techniques such as an exclusive endoscopic approach can now be used, ensuring a simpler postoperative course. However, these techniques require a thorough knowledge of frontal sinus anatomy and endoscopic CSF leak repair. This knowledge is essential both to ensure closure of the CSF leak and to preserve frontal sinus patency. PMID:26363602

  1. Lumbar cerebrospinal fluid concentrations of somatostatin and neuropeptide Y in multiple sclerosis

    SciTech Connect

    Vecsei, L.; Csala, B.; Widerloev, E.E.; Ekman, R.; Czopf, J.; Palffy, G. )

    1990-09-01

    The cerebrospinal fluid (CSF) concentrations of somatostatin and neuropeptide Y were investigated by use of radioimmunoassay in patients suffering from chronic progressive multiple sclerosis. The somatostatin level was significantly decreased in the CSF of patients with multiple sclerosis compared to the control group. The magnitude of this change was more pronounced in patients with severe clinical symptoms of the illness. The CSF neuropeptide Y concentration did not differ from the control values. These findings suggest a selective involvement of somatostatin neurotransmission in multiple sclerosis.

  2. Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease.

    PubMed

    Formisano, P; Aldridge, B; Alony, Y; Beekhuis, L; Davies, E; Del Pozo, J; Dunn, K; English, K; Morrison, L; Sargison, N; Seguino, A; Summers, B A; Wilson, D; Milne, E; Beard, P M

    2013-03-31

    Protozoal merozoites were identified in the cerebrospinal fluid of two sheep with neurological disease in the UK. Polymerase chain reaction (PCR) identified the merozoites as Sarcocystis capracanis, a common protozoal pathogen of goats. This is the first report of this species infecting sheep and may represent an aberrant infection with sheep acting as dead end hosts, or alternatively could indicate that sheep are able to act as intermediate hosts for S. capracanis, widening the previously reported host range of this pathogen. It is possible that S. capracanis is a previously unrecognised cause of ovine protozoal meningoencephalitis (OPM) in the UK. PMID:23312871

  3. Delayed cerebrospinal fluid rhinorrhea four years after gamma knife surgery for juvenile angiofibroma.

    PubMed

    Min, Hyun Jin; Chung, Hyo Jin; Kim, Chang-Hoon

    2014-11-01

    Juvenile angiofibroma (JA) is a highly vascularized tumor that often recurs or regrows. Recently, gamma knife surgery (GKS) was attempted on unresectable or remnant JA. We experienced a JA case that developed cerebrospinal fluid (CSF) rhinorrhea 4 years after GKS. Two surgical excisions using midfacial degloving approach were performed before GKS. After radiosurgery, the tumor was controlled, and no early complications were observed. However, 4 years after, intractable CSF leakage developed as a late complication, and we thus performed 4 subsequent endoscopic surgical repairs. The CSF leakage is very rare but can occur as a late complication of GKS and should be treated aggressively. PMID:25377982

  4. Penetration of dihydroartemisinin into cerebrospinal fluid after administration of intravenous artesunate in severe falciparum malaria.

    PubMed

    Davis, Timothy M E; Binh, Tran Quang; Ilett, Kenneth F; Batty, Kevin T; Phuöng, Hoang Lan; Chiswell, Gregory M; Phuong, Vu Duong Bich; Agus, Cindy

    2003-01-01

    Penetration of cerebrospinal fluid (CSF) by artesunate and DHA was assessed in six adults with cerebral or severe malaria. Lumbar punctures were performed on admission and during convalescence, at 15 min (patient 1), 30 min (patient 2), 45 min (patient 3), 60 min (patient 4), 90 min (patient 5), and 120 min (patient 6) after intravenous administration of 120 mg of artesunate. No artesunate was detectable in CSF. In both studies, DHA levels in CSF increased with time while dihydroartemisinin levels in plasma fell. Dihydroartemisinin might accumulate in CSF during frequent artesunate dosing. PMID:12499215

  5. Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys

    SciTech Connect

    Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.

    1984-05-01

    Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption.

  6. Cerebrospinal fluid from rats given hypoxic preconditioning protects neurons from oxygen-glucose deprivation-induced injury

    PubMed Central

    Zhang, Yan-bo; Guo, Zheng-dong; Li, Mei-yi; Li, Si-jie; Niu, Jing-zhong; Yang, Ming-feng; Ji, Xun-ming; Lv, Guo-wei

    2015-01-01

    Hypoxic preconditioning activates endogenous mechanisms that protect against cerebral ischemic and hypoxic injury. To better understand these protective mechanisms, adult rats were housed in a hypoxic environment (8% O2/92% N2) for 3 hours, and then in a normal oxygen environment for 12 hours. Their cerebrospinal fluid was obtained to culture cortical neurons from newborn rats for 1 day, and then the neurons were exposed to oxygen-glucose deprivation for 1.5 hours. The cerebrospinal fluid from rats subjected to hypoxic preconditioning reduced oxygen-glucose deprivation-induced injury, increased survival rate, upregulated Bcl-2 expression and downregulated Bax expression in the cultured cortical neurons, compared with control. These results indicate that cerebrospinal fluid from rats given hypoxic preconditioning protects against oxygen-glucose deprivation-induced injury by affecting apoptosis-related protein expression in neurons from newborn rats. PMID:26604909

  7. Cerebrospinal Fluid ?-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

    PubMed Central

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C.; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2015-01-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although ?-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and ?-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess ?-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing ?-synuclein (phase 1 to phase 2 change of ?0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between ?-synuclein and motor symptoms. Longitudinally, lower ?-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall ?-synuclein × time interaction effect coefficient, ?0.12 (P = 0.037); delayed recall, ?0.05 (P = 0.002); New Dot Test, ?0.03 (P = 0.002)]. Thus, ?-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  8. Evaluation of three tracers for labeling distal cerebrospinal fluid-contacting neurons.

    PubMed

    Zhou, Fang; Wang, Jiayou; Zhang, Hongxing; Liu, He; Zhao, Guangping; Zu, Cuihua; Lu, Xiaoxing; Zhang, Licai

    2013-10-01

    It has been reported that distal cerebrospinal fluid-contacting neurons (dCSF-CNs) can be detected by immunohistochemical assay using cholera toxin subunit B-conjugated horseradish peroxidase (CB-HRP). In the present study, another two methods with CB alone or CB-conjugated FITC (CB-FITC) were used, and the results from the three methods were compared. Adult Sprague-Dawley rats were randomly divided into three groups with CB-HRP, CB or CB-FITC. Tracers were diluted to 30% in artificial cerebrospinal fluid and injected separately (in a volume of 3 ?L) into the lateral ventricle. Animals from the CB-HRP and CB groups were perfused 48 h after surgery while animals from the CB-FITC group were perfused 1, 3, 6, 12, 24 or 48 h after surgery. The brain was sectioned (40 ?m) for immunofluorescence and five sections with positive neurons were selected from each rat for neuron counting. Three clusters of positive neurons in a 'Y-like' distribution were detected ventral to the cerebral aqueduct of rats from the three groups. No significant difference was observed among the quantitative data. In the CB-FITC group, stable staining was detected even at 6 h after injection. Taken together, lateral ventricle injection of CB/CB-FITC is a useful method for labeling dCSF-CNs in rats. The CB-FITC method makes dCSF-CNs labeling much simpler and more convenient. PMID:23585297

  9. Therapeutic implications of the choroid plexus-cerebrospinal fluid interface in neuropsychiatric disorders.

    PubMed

    Demeestere, Delphine; Libert, Claude; Vandenbroucke, Roosmarijn E

    2015-11-01

    The choroid plexus (CP) comprises an epithelial monolayer that forms an important physical, enzymatic and immunologic barrier, called the blood-cerebrospinal fluid barrier (BCSFB). It is a highly vascularized organ located in the brain ventricles that is key in maintaining brain homeostasis as it produces cerebrospinal fluid (CSF) and has other important secretory functions. Furthermore, the CP-CSF interface plays a putative role in neurogenesis and has been implicated in neuropsychiatric diseases such as the neurodevelopmental disorders schizophrenia and autism. A role for this CNS border was also implicated in sleep disturbances and chronic and/or severe stress, which are risk factors for the development of neuropsychiatric conditions. Understanding the mechanisms by which disturbance of the homeostasis at the CP-CSF interface is involved in these different chronic low-grade inflammatory diseases can give new insights into therapeutic strategies. Hence, this review discusses the different roles that have been suggested so far for the CP in these neuropsychiatric disorders, with special attention to potential therapeutic applications. PMID:26116435

  10. Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders.

    PubMed

    Maxeiner, Horst-G; Rojewski, Markus Thomas; Schmitt, Anita; Tumani, Hayrettin; Bechter, Karl; Schmitt, Michael

    2009-01-01

    Recent studies suggest inflammatory mechanisms involved in the pathogenesis of major psychiatric disorders (MPD). T cells play a major role during inflammation, but little is known about T cell subpopulations in the cerebrospinal fluid (CSF). We investigated the frequency of cells positive for the surface markers CD4, CD8, CD25, CD45, CD69, and CD127 in 45 paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples by multiparameter flow cytometry from patients with MPD of the schizophrenic and affective spectrum with normal CSF cell counts and compared them with those from patients with non-inflammatory (NIND), chronic inflammatory (CIND) neurological disorders, and meningitis (MEN). In MEN patients, CD4+ cell frequency in PB, but not in CSF, was significantly increased as compared to CIND and NIND. No difference between patient groups was observed for CD8+. CD4+CD45RO+ double positive cells in PB were significantly lower in CIND than in MEN or NIND. The frequency of CD4+CD25+ cells in PB was significantly higher in MEN than in MPD or CIND. For CSF, the percentage of CD4+CD127(dim) cells was significantly lower in MEN than in MPD. CD4+CD127(dim) in PB and CSF showed overlapping characteristic clusters between MPD and CIND and MEN patients. Overall, the hypothesis of low degree inflammation in a subgroup of MPD is supported. The analysis of lymphocyte subsets in PB and CSF constitutes a novel promising tool to understand underlying pathomechanisms in psychiatric and neurological disorders on an individual case level. PMID:18771722

  11. A Rare Coexistence: Drug Induced Hepatitis and Meningitis in Association With Ibuprofen

    PubMed Central

    Nayudu, Suresh Kumar; Kavuturu, Shilpa; Niazi, Masooma; Daniel, Myrta; Dev, Anil; Kumbum, Kavitha

    2013-01-01

    Ibuprofen, a commonly used NSAID is reported to be associated with drug induced liver injury. Ibuprofen is also known to be associated with drug-induced meningitis especially in patients with connective tissue disorders. However presentation of hepatitis and meningitis in association with Ibuprofen use in the same individual has never been reported. We present a case of young woman who developed abnormal liver chemistries and neurological symptoms while on Ibuprofen. Her liver biopsy findings were suggestive of drug induced liver injury and cerebrospinal fluid analysis was suggestive of aseptic meningitis. Clinical and biochemical improvement was noted on cessation of Ibuprofen. PMID:23671551

  12. Membrane-Introduction Mass Spectrometry Analysis of Desflurane, Propofol and Fentanyl in Plasma and Cerebrospinal Fluid for Estimation BBB Properties

    PubMed Central

    Cherebillo, Vyacheslav Yu.; Polegaev, Andrei V.

    2015-01-01

    A possibility to use the Membrane-Introduction Mass Spectrometry (MIMS) with membrane separator interface has evolved into a powerful method for measurement of anaesthetic agents absolute concentration in blood plasma and cerebrospinal fluid for the study of blood-brain barrier (BBB) properties. Recent advanced a new membrane material was used for drug concentration measurement in biologic fluids. A hydrophobic membrane was used in the interface to separate anaesthetic agents from biological fluids: inhalational anaesthetic desflurane,hypnotic propofol, analgesic fentanyl. The selective detection of volatile anesthetic agents in blood does not require long-term sample processing before injecting the sample into mass-spectrometer interface, in contrast to chromatographic methods. Mass-spectrometric interface for the measurement of anaesthetic agent concentration in biological fluids (blood plasma and cerebrospinal fluid) is described. Sampling of biological fluids was performed during balanced inhalational (desflurane, fentanyl) anaesthesia and total intravenous (propofol, fentanyl) anaesthesia. PMID:26412969

  13. Membrane-Introduction Mass Spectrometry Analysis of Desflurane, Propofol and Fentanyl in Plasma and Cerebrospinal Fluid for Estimation BBB Properties.

    PubMed

    Cherebillo, Vyacheslav Yu; Elizarov, Andrei Yu; Polegaev, Andrei V

    2015-09-01

    A possibility to use the Membrane-Introduction Mass Spectrometry (MIMS) with membrane separator interface has evolved into a powerful method for measurement of anaesthetic agents absolute concentration in blood plasma and cerebrospinal fluid for the study of blood-brain barrier (BBB) properties. Recent advanced a new membrane material was used for drug concentration measurement in biologic fluids. A hydrophobic membrane was used in the interface to separate anaesthetic agents from biological fluids: inhalational anaesthetic desflurane,hypnotic propofol, analgesic fentanyl. The selective detection of volatile anesthetic agents in blood does not require long-term sample processing before injecting the sample into mass-spectrometer interface, in contrast to chromatographic methods. Mass-spectrometric interface for the measurement of anaesthetic agent concentration in biological fluids (blood plasma and cerebrospinal fluid) is described. Sampling of biological fluids was performed during balanced inhalational (desflurane, fentanyl) anaesthesia and total intravenous (propofol, fentanyl) anaesthesia. PMID:26412969

  14. Reassessing cerebrospinal fluid (CSF) hydrodynamics: a literature review presenting a novel hypothesis for CSF physiology.

    PubMed

    Chikly, Bruno; Quaghebeur, Jörgen

    2013-07-01

    The traditional model of cerebrospinal fluid (CSF) hydrodynamics is being increasingly challenged in view of recent scientific evidences. The established model presumes that CSF is primarily produced in the choroid plexuses (CP), then flows from the ventricles to the subarachnoid spaces, and is mainly reabsorbed into arachnoid villi (AV). This model is seemingly based on faulty research and misinterpretations. This literature review presents numerous evidence for a new hypothesis of CSF physiology, namely, CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit. IF and CSF are mainly formed and reabsorbed across the walls of CNS blood capillaries. CP, AV and lymphatics become minor sites for CSF hydrodynamics. The lymphatics may play a more significant role in CSF absorption when CSF-IF pressure increases. The consequences of this complete reformulation of CSF hydrodynamics may influence applications in research, publications, including osteopathic manual treatments. PMID:23768280

  15. Leukocyte attraction by CCL20 and its receptor CCR6 in humans and mice with pneumococcal meningitis.

    PubMed

    Klein, Matthias; Brouwer, Matthijs C; Angele, Barbara; Geldhoff, Madelijn; Marquez, Gabriel; Varona, Rosa; Häcker, Georg; Schmetzer, Helga; Häcker, Hans; Hammerschmidt, Sven; van der Ende, Arie; Pfister, Hans-Walter; van de Beek, Diederik; Koedel, Uwe

    2014-01-01

    We previously identified CCL20 as an early chemokine in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis but its functional relevance was unknown. Here we studied the role of CCL20 and its receptor CCR6 in pneumococcal meningitis. In a prospective nationwide study, CCL20 levels were significantly elevated in the CSF of patients with pneumococcal meningitis and correlated with CSF leukocyte counts. CCR6-deficient mice with pneumococcal meningitis and WT mice with pneumococcal meningitis treated with anti-CCL20 antibodies both had reduced CSF white blood cell counts. The reduction in CSF pleocytosis was also accompanied by an increase in brain bacterial titers. Additional in vitro experiments showed direct chemoattractant activity of CCL20 for granulocytes. In summary, our results identify the CCL20-CCR6 axis as an essential component of the innate immune defense against pneumococcal meningitis, controlling granulocyte recruitment. PMID:24699535

  16. Blood-cerebrospinal fluid barrier dysfunction in patients with bipolar disorder in relation to antipsychotic treatment.

    PubMed

    Zetterberg, Henrik; Jakobsson, Joel; Redsäter, Mikael; Andreasson, Ulf; Pålsson, Erik; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette Gm; Blennow, Kaj; Landén, Mikael

    2014-07-30

    Blood-cerebrospinal barrier (BCB) dysfunction has previously been shown in subjects with schizophrenia and depressed patients with attempted suicide. Bipolar disorder (BPD) shares clinical features with both these disorders, but it is unknown if the integrity of the BCB is altered also in BPD. To assess if BCB function in BPD we surveyed 134 mood-stabilized BPD patients and 86 healthy controls. Serum and cerebrospinal fluid (CSF) samples were collected and analyzed for albumin concentration by immunonephelometry. CSF/serum albumin ratio, an established measure of BCB function, was significantly elevated in BPD patients as compared to controls. After stratifying patients according to diagnostic subtype, BPD I patients had the highest CSF/serum albumin ratios. Moreover, BPD patients on antipsychotic treatment had higher CSF/serum albumin ratio than BPD patients on other treatments. When excluding BPD patients on antipsychotic treatment the difference in CSF/serum albumin ratio between the BPD and control groups disappeared. In conclusion, antipsychotic treatment in BPD is associated with elevated CSF/serum albumin ratio, tentatively as a sign of impaired BCB function. Whether this elevation is caused by antipsychotic treatment or is associated with a certain subtype of BPD, requiring antipsychotic treatment, remains to be determined. PMID:24745469

  17. Etiology of aseptic meningitis and clinical characteristics in immune-competent adults.

    PubMed

    Han, Su-Hyun; Choi, Hye-Yeon; Kim, Jeong-Min; Park, Kwang-Ryul; Youn, Young Chul; Shin, Hae-Won

    2016-01-01

    Viral meningitis is the most common cause of aseptic meningitis. Use of the polymerase chain reaction (PCR) has increased the ability to determine the etiology of viral meningitis. This study used PCR analysis to evaluate the etiology of aseptic meningitis in 177 previously healthy adults over a 5-year period, as well as analyzing the clinical characteristics, cerebrospinal fluid (CSF) findings, and prognosis according to each etiology. The most frequent cause of aseptic meningitis was enterovirus (EV), followed by varicella zoster virus (VZV). Patients with EV meningitis were significantly younger than those with VZV meningitis. The percentage of lymphocytes in white blood cell counts and protein concentrations in the CSF differed significantly among patients with EV, VZV and meningitis of undetermined etiology. Younger age and lower percentage of lymphocyte and protein level in CSF analysis may be suggestive of EV meningitis. Further prospective studies are warranted to identify the correlations between the clinical characteristics and the etiologies of meningitis. J. Med. Virol. 88:175-179, 2016. © 2015 Wiley Periodicals, Inc. PMID:26118835

  18. Clinical features, Outcomes and Molecular Profiles of Drug Resistance in Tuberculous Meningitis in non-HIV Patients.

    PubMed

    Zhang, Jingya; Hu, Xuejiao; Hu, Xin; Ye, Yuanxin; Shang, Mengqiao; An, Yunfei; Gou, Haimei; Zhao, Zhenzhen; Peng, Wu; Song, Xingbo; Zhou, Yanhong; Kang, Mei; Xie, Yi; Chen, Xuerong; Lu, Xiaojun; Ying, Binwu; Wang, Lanlan

    2016-01-01

    Tuberculous meningitis continues to be a serious problem for physicians because it is difficult to make an early diagnosis and the consequences of delaying treatment are severe. The objective of this study is to provide data for the optimization of diagnostic and timely treatment of tuberculous meningitis. Of the 401 human immunodeficiency virus (HIV)-negative tuberculous meningitis patients in our study, 332 were found to have an impaired blood brain barrier (82.8%). Nearly 17.0% of patients failed to be timely diagnosed. Headache (53.6%) and fever (48.6%) were the most common features, and Computed Tomography/Magnetic Resonance Imaging (CT/MRI) detected 96 patients (23.9%) with abnormal meningeal imaging. Cerebrospinal fluid real-time polymerase chain reaction was positive in 73.8% of the tuberculous meningitis patients, whereas, smears and cultures detected only 6.7% and 5.2%, respectively. Further analysis identified striking differences between drug-resistant and drug-susceptible tuberculous meningitis. Patients with drug resistance correlated with grave prognosis. Tuberculous meningitis diagnosis should overall embody clinical symptoms, laboratory and cerebral imaging findings, and more sensitive diagnostic approaches are still warranted. Our data suggest cerebrospinal fluid polymerase chain reaction for mycobacterial DNA and molecular drug susceptibility testing as routine assays for suspected tuberculous meningitis patients, and observation of the blood brain barrier function could be performed for individual management. PMID:26738994

  19. Stable concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid during 2 years of therapy.

    PubMed

    van Praag, Rieneke M E; van Weert, Elisabeth C M; van Heeswijk, Rolf P G; Zhou, Xiao-Jian; Sommadossi, Jean-Pierre; Jurriaans, Suzanne; Lange, Joep M A; Hoetelmans, Richard M W; Prins, Jan M

    2002-03-01

    For a number of antiretroviral drugs, prolonged suppression of viral replication is related to drug exposure. Therefore, it is important to maintain stable concentrations during prolonged therapy. While studies suggest that saquinavir concentrations decrease over time, we show that concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid are stable during 2 years of therapy. PMID:11850283

  20. Stable Concentrations of Zidovudine, Stavudine, Lamivudine, Abacavir, and Nevirapine in Serum and Cerebrospinal Fluid during 2 Years of Therapy

    PubMed Central

    van Praag, Rieneke M. E.; van Weert, Elisabeth C. M.; van Heeswijk, Rolf P. G; Zhou, Xiao-Jian; Sommadossi, Jean-Pierre; Jurriaans, Suzanne; Lange, Joep M. A.; Hoetelmans, Richard M. W.; Prins, Jan M.

    2002-01-01

    For a number of antiretroviral drugs, prolonged suppression of viral replication is related to drug exposure. Therefore, it is important to maintain stable concentrations during prolonged therapy. While studies suggest that saquinavir concentrations decrease over time, we show that concentrations of zidovudine, stavudine, lamivudine, abacavir, and nevirapine in serum and cerebrospinal fluid are stable during 2 years of therapy. PMID:11850283

  1. A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies

    PubMed Central

    Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P.; Alder, Hansjuerg; Carosi, Mariantonia A.; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M.

    2015-01-01

    Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application. The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies. CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization. Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies. This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications. PMID:26246487

  2. Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat

    SciTech Connect

    Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J. )

    1990-01-01

    Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function.

  3. Effects of spatial variation of skull and cerebrospinal fluid layers on optical mapping of brain activities

    NASA Astrophysics Data System (ADS)

    Wang, Shuping; Shibahara, Nanae; Kuramashi, Daishi; Okawa, Shinpei; Kakuta, Naoto; Okada, Eiji; Maki, Atsushi; Yamada, Yukio

    2010-07-01

    In order to investigate the effects of anatomical variation in human heads on the optical mapping of brain activity, we perform simulations of optical mapping by solving the photon diffusion equation for layered-models simulating human heads using the finite element method (FEM). Particularly, the effects of the spatial variations in the thicknesses of the skull and cerebrospinal fluid (CSF) layers on mapping images are investigated. Mapping images of single active regions in the gray matter layer are affected by the spatial variations in the skull and CSF layer thicknesses, although the effects are smaller than those of the positions of the active region relative to the data points. The increase in the skull thickness decreases the sensitivity of the images to active regions, while the increase in the CSF layer thickness increases the sensitivity in general. The images of multiple active regions are also influenced by their positions relative to the data points and by their depths from the skin surface.

  4. Measurement of flow of cerebrospinal fluid in shunts by transcutaneous thermal convection. Technical note.

    PubMed

    Neff, Samuel

    2005-10-01

    With the goal of developing a practical method of performing noninvasive measurements of flow in cerebrospinal fluid (CSF) shunts, transcutaneous thermal convection CSF shunt flow measurement was investigated using dimensional analysis, numerical modeling, and bench testing. Using appropriate manufacturing practices and controls, a microcontroller-based device was designed, constructed, and clinically tested. Flow was detected in functioning shunts nine times in 10 attempts. One test failed due to postoperative edema, and subsequent testing was limited to patients who had not undergone shunt surgery within the previous 2 weeks. On the basis of these data and previous reports, 510(k) clearance was granted by the Food and Drug Administration for detection of flow in CSF shunts. Flow in CSF shunts can be detected noninvasively and cost effectively by using a simple thermal convection system. The positive and negative predictive values of the test are equal to or greater than those of brain imaging and radionuclide shunt studies. PMID:16270690

  5. Resistance to outflow of cerebrospinal fluid after central infusions of angiotensin

    NASA Technical Reports Server (NTRS)

    Morrow, B. A.; Keil, L. C.; Severs, W. B.

    1992-01-01

    Infusions of artificial cerebrospinal fluid (CSF) into the cerebroventricles of conscious rats can raise CSF pressure (CSFp). This response can be modified by some neuropeptides. One of these, angiotensin, facilitates the rise in CSFp. We measured CSFp in conscious rats with a computerized system and evaluated resistance to CSF outflow during infusion of artificial CSF, with or without angiotensin, from the decay kinetics of superimposed bolus injections. Angiotensin (10 ng/min) raised CSFp (P less than 0.05) compared with solvent, but the resistance to CSF outflow of the two groups was similar (P greater than 0.05). Because CSFp was increased by angiotensin without an increase in the outflow resistance, a change in some volume compartment is likely. Angiotensin may raise CSFp by increasing CSF synthesis; this possibility is supported, since the choroid plexuses contain an intrinsic isorenin-angiotensin system. Alternatively, angiotensin may dilate pial arteries, leading to an increased intracranial blood volume.

  6. Oligoclonal bands in cerebrospinal fluid detected by PhastSystem isoelectric focusing.

    PubMed

    Wybo, I; Van Blerk, M; Malfait, R; Goubert, P; Gorus, F

    1990-01-01

    Pharmacia's "PhastSystem" for semi-automated isoelectric focusing (IEF) in thin precast polyacrylamide gels (PAGE) was found to be as sensitive as high-resolution protein electrophoresis (HRPE) in agarose gels and conventional PAGE-IEF for detection of oligoclonal banding (OB) in concentrated cerebrospinal fluid (CSF) samples. Both PhastSystem IEF and HRPE revealed OB in CSF from eight of nine multiple sclerosis patients and four of 10 patients with various types of infection of the central nervous system as opposed to only two of 70 patients with miscellaneous neuropsychiatric disorders. The PhastSystem also frequently detected OB in silver-stained, unconcentrated CSF from patients with multiple sclerosis. PMID:1688744

  7. Cerebrospinal fluid constituents of cat vary with susceptibility to motion sickness

    NASA Technical Reports Server (NTRS)

    Lucot, James B.; Crampton, George H.; Matson, Wayne R.; Gamache, Paul H.

    1989-01-01

    The cerebrospinal fluid drawn from the fourth ventricles of the brains of cats during and after the development of motion sickness was studied to determine what neurotransmitters may be involved in the development of the sickness. The analytical procedure, which uses HPLC coupled with n-electrode coulometric electrochemical detection to measure many compounds with picogram sensitivity, is described. Baseline levels of DOPAC, MHPGSO4, uric acid, DA, 5-HIAA, and HVA were lower on motion and control days in cats which became motion sick when compared with cats which did not. None of the total of 36 identified compounds identified in the samples varied as a function of either exposure to motion or provocation of emesis. It is concluded that susceptibility to motion sickness is a manifestation of individual differences related to fundamental neurochemical composition.

  8. Antibodies to varicella zoster virus in the cerebrospinal fluid of neonates with seizures.

    PubMed

    Mustonen, K; Mustakangas, P; Smeds, M; Mannonen, L; Uotila, L; Vaheri, A; Koskiniemi, M

    1998-01-01

    Four neonates with convulsions had IgG antibodies in their cerebrospinal fluid (CSF) to varicella zoster virus (VZV). These antibodies were found in the sera of two of these patients after the age of 6 months. Antibodies to 16 different microbes were studied from the serum and CSF of 201 neonates with neurological problems. The presence of DNA specific to HSV-1, HSV-2, and VZV in the CSF was also investigated using the polymerase chain reaction (PCR). Antibodies to VZV were detected in the CSF of four neonates. Antibody indices suggested production of VZV specific antibodies in the central nervous system. These findings suggest that intrathecal production of antibodies to VZV can appear in neonates with neurological problems, which suggests that intrauterine VZV infection can be acquired without cutaneous symptoms in the mother. PMID:9536843

  9. Cerebrospinal fluid progranulin levels in patients with different multiple sclerosis subtypes.

    PubMed

    De Riz, Milena; Galimberti, Daniela; Fenoglio, Chiara; Piccio, Laura M; Scalabrini, Diego; Venturelli, Eliana; Pietroboni, Anna; Piola, Mirko; Naismith, Robert T; Parks, Becky J; Fumagalli, Giorgio; Bresolin, Nereo; Cross, Anne H; Scarpini, Elio

    2010-01-22

    Progranulin has recently attracted attention due to the discovery of mutations in its encoding gene (GRN) in several cases of frontotemporal lobar degeneration, but also for a possible role in inflammatory processes. In adult central nervous system, GRN mRNA is expressed in forebrain, olfactory bulbs and spinal cord. Progranulin cerebrospinal fluid (CSF) levels were evaluated in 55 patients with multiple sclerosis (MS) as well as in 35 subjects with non-inflammatory neurological diseases (NIND), 7 individuals with other inflammatory neurological disease (OIND) and 8 controls (CON), matched for ethnic background, gender and age. No statistically significant differences were found in patients compared with either NIND, OIND or CON (P>0.05), even stratifying according to disease subtype or gender. A positive correlation between progranulin CSF levels and age was observed in patients (rho=0.29, P=0.03). According to these data, progranulin does not likely play a major role in the pathogenesis of MS. PMID:19963041

  10. Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation

    SciTech Connect

    Meyer, J.S.; Tachibana, H.; Hardenberg, J.P.; Dowell, R.E. Jr.; Kitagawa, Y.; Mortel, K.F.

    1984-02-01

    Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

  11. Human Immunodeficiency Virus-associated primary effusion lymphoma: An exceedingly rare entity in cerebrospinal fluid

    PubMed Central

    Jain, Sarika; Palekar, Alka; Monaco, Sara E.; Craig, Fiona E.; Bejjani, Ghassan; Pantanowitz, Liron

    2015-01-01

    Primary effusion lymphoma (PEL) in patients with Human Immunodeficiency Virus (HIV) infection may involve pleural, pericardial, and peritoneal cavities. PEL involving the cerebrospinal fluid (CSF) is exceedingly rare, and to our knowledge has only been reported in two cases. We report another case of PEL diagnosed in CSF from a 61-year-old male with Acquired Immunodeficiency Syndrome that presented with neurological symptoms. Imaging studies of his brain showed leptomeningeal/periventricular enhancement, but no mass lesion. His CSF demonstrated human herpesvirus-8 positive pleomorphic lymphoplasmacytoid cells of null cell phenotype. This case highlights that albeit rare, PEL should be included in the differential diagnosis when large atypical cells are encountered in CSF of HIV-positive patients, even when such patients have no history of lymphoma. As in this case, ancillary studies are required to make an accurate diagnosis of PEL in CSF cytology. PMID:26604975

  12. "Tear drops" in the cerebrospinal fluid: Correct by scatter, but pathognomonic by site.

    PubMed

    Mittal, Reena; Chopra, Anita; Soni, Sushant; Bakhshi, Sameer; Kumar, Rajive

    2015-01-01

    Extramedullary relapse in acute promyelocytic leukemia (APL) is rare, but occurs most commonly in central nervous system (CNS), generally in high-risk cases (total leucocyte count?10,000/µL, atypical morphology or disseminated intravascular coagulation at presentation), and concomitant with bone marrow (BM) relapse. Here, we describe a case of APL who except for CD56 positivity was low risk but had a CNS relapse without concomitant BM involvement. Diagnosis of isolated CNS relapse was based on characteristic tear-drop pattern for CD45/side scatter plot on flow cytometry, a full compatible immunophenotype and cytomorphology in the cerebrospinal fluid. The case illustrates the value of the latter and the importance of including CD56 in risk assessment of APL. PMID:25257969

  13. Identification of biomarkers in cerebrospinal fluid and serum of multiple sclerosis patients by immunoproteomics approach.

    PubMed

    Colomba, Paolo; Fontana, Simona; Salemi, Giuseppe; Barranca, Marilisa; Lo Sicco, Claudia; Mazzola, Maria Antonietta; Ragonese, Paolo; Savettieri, Giovanni; De Leo, Giacomo; Alessandro, Riccardo; Duro, Giovanni

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these. PMID:25517032

  14. Identification of Biomarkers in Cerebrospinal Fluid and Serum of Multiple Sclerosis Patients by Immunoproteomics Approach

    PubMed Central

    Colomba, Paolo; Fontana, Simona; Salemi, Giuseppe; Barranca, Marilisa; Lo Sicco, Claudia; Mazzola, Maria Antonietta; Ragonese, Paolo; Savettieri, Giovanni; De Leo, Giacomo; Alessandro, Riccardo; Duro, Giovanni

    2014-01-01

    Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. At present, the molecular mechanisms causing the initiation, development and progression of MS are poorly understood, and no reliable proteinaceous disease markers are available. In this study, we used an immunoproteomics approach to identify autoreactive antibodies in the cerebrospinal fluid of MS patients to use as candidate markers with potential diagnostic value. We identified an autoreactive anti-transferrin antibody that may have a potential link with the development and progression of MS. We found this antibody at high levels also in the serum of MS patients and created an immunoenzymatic assay to detect it. Because of the complexity and heterogeneity of multiple sclerosis, it is difficult to find a single marker for all of the processes involved in the origin and progression of the disease, so the development of a panel of biomarkers is desirable, and anti-transferrin antibody could be one of these. PMID:25517032

  15. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE

    PubMed Central

    Ayton, Scott; Faux, Noel G.; Bush, Ashley I.; Weiner, Michael W.; Aisen, Paul; Petersen, Ronald; Jack Jr., Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Khachaturian, Zaven; Sorensen, Greg; Kuller, Lew; Raichle, Marc; Paul, Steven; Davies, Peter; Fillit, Howard; Hefti, Franz; Holtzman, Davie; Marcel Mesulam, M.; Potter, William; Snyder, Peter; Schwartz, Adam; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; Sather, Tamie; Jiminez, Gus; Harvey, Danielle; Bernstein, Matthew; Fox, Nick; Thompson, Paul; Schuff, Norbert; Borowski, Bret; Gunter, Jeff; Senjem, Matt; Vemuri, Prashanthi; Jones, David; Kantarci, Kejal; Ward, Chad; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Mathis, Chet; Landau, Susan; Cairns, Nigel J.; Householder, Erin; Taylor-Reinwald, Lisa; Lee, Virginia; Korecka, Magdalena; Figurski, Michal; Crawford, Karen; Neu, Scott; Foroud, Tatiana M.; Potkin, Steven; Shen, Li; Faber, Kelley; Kim, Sungeun; Nho, Kwangsik; Thal, Leon; Buckholtz, Neil; Albert, Marylyn; Frank, Richard; Hsiao, John; Kaye, Jeffrey; Quinn, Joseph; Lind, Betty; Carter, Raina; Dolen, Sara; Schneider, Lon S.; Pawluczyk, Sonia; Beccera, Mauricio; Teodoro, Liberty; Spann, Bryan M.; Brewer, James; Vanderswag, Helen; Fleisher, Adam; Heidebrink, Judith L.; Lord, Joanne L.; Mason, Sara S.; Albers, Colleen S.; Knopman, David; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Rountree, Susan; Dang, Mimi; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Ances, Beau; Carroll, Maria; Leon, Sue; Mintun, Mark A.; Schneider, Stacy; Oliver, Angela; Marson, Daniel; Griffith, Randall; Clark, David; Geldmacher, David; Brockington, John; Roberson, Erik; Grossman, Hillel; Mitsis, Effie; deToledo-Morrell, Leyla; Shah, Raj C.; Duara, Ranjan; Varon, Daniel; Greig, Maria T.; Roberts, Peggy; Albert, Marilyn; Onyike, Chiadi; D'Agostino II, Daniel; Kielb, Stephanie; Galvin, James E.; Cerbone, Brittany; Michel, Christina A.; Rusinek, Henry; de Leon, Mony J; Glodzik, Lidia; De Santi, Susan; Murali Doraiswamy, P.; Petrella, Jeffrey R.; Wong, Terence Z.; Arnold, Steven E.; Karlawish, Jason H.; Wolk, David; Smith, Charles D.; Jicha, Greg; Hardy, Peter; Sinha, Partha; Oates, Elizabeth; Conrad, Gary; Lopez, Oscar L.; Oakley, MaryAnn; Simpson, Donna M.; Porsteinsson, Anton P.; Goldstein, Bonnie S.; Martin, Kim; Makino, Kelly M.; Saleem Ismail, M.; Brand, Connie; Mulnard, Ruth A.; Thai, Gaby; Mc-Adams-Ortiz, Catherine; Womack, Kyle; Mathews, Dana; Quiceno, Mary; Diaz-Arrastia, Ramon; King, Richard; Weiner, Myron; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Swerdlow, Russell H.; Apostolova, Liana; Tingus, Kathleen; Woo, Ellen; Silverman, Daniel H.S.; Lu, Po H.; Bartzokis, George; Graff-Radford, Neill R; Parfitt, Francine; Kendall, Tracy; Johnson, Heather; Farlow, Martin R.; Hake, Ann Marie; Matthews, Brandy R.; Herring, Scott; Hunt, Cynthia; van Dyck, Christopher H.; Carson, Richard E.; MacAvoy, Martha G.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Stefanovic, Bojana; Caldwell, Curtis; Robin Hsiung, Ging-Yuek; Feldman, Howard; Mudge, Benita; Assaly, Michele; Kertesz, Andrew; Rogers, John; Bernick, Charles; Munic, Donna; Kerwin, Diana; Mesulam, Marek-Marsel; Lipowski, Kristine; Wu, Chuang-Kuo; Johnson, Nancy; Sadowsky, Carl; Martinez, Walter; Villena, Teresa; Scott Turner, Raymond; Johnson, Kathleen; Reynolds, Brigid; Sperling, Reisa A.; Johnson, Keith A.; Marshall, Gad; Frey, Meghan; Lane, Barton; Rosen, Allyson; Tinklenberg, Jared; Sabbagh, Marwan N.; Belden, Christine M.; Jacobson, Sandra A.; Sirrel, Sherye A.; Kowall, Neil; Killiany, Ronald; Budson, Andrew E.; Norbash, Alexander; Johnson, Patricia Lynn; Allard, Joanne; Lerner, Alan; Ogrocki, Paula; Hudson, Leon; Fletcher, Evan; Carmichael, Owen; Olichney, John; DeCarli, Charles; Kittur, Smita; Borrie, Michael; Lee, T-Y; Bartha, Rob; Johnson, Sterling; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Preda, Adrian; Nguyen, Dana; Tariot, Pierre; Reeder, Stephanie; Bates, Vernice; Capote, Horacio; Rainka, Michelle; Scharre, Douglas W.; Kataki, Maria; Adeli, Anahita; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Pearlson, Godfrey D.; Blank, Karen; Anderson, Karen; Santulli, Robert B.; Kitzmiller, Tamar J.; Schwartz, Eben S.; Sink, Kaycee M.; Williamson, Jeff D.; Garg, Pradeep; Watkins, Franklin; Ott, Brian R.; Querfurth, Henry; Tremont, Geoffrey

    2015-01-01

    Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-?4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-?4 being the major genetic risk factor for AD. PMID:25988319

  16. Ferritin levels in the cerebrospinal fluid predict Alzheimer's disease outcomes and are regulated by APOE.

    PubMed

    Ayton, Scott; Faux, Noel G; Bush, Ashley I

    2015-01-01

    Brain iron elevation is implicated in Alzheimer's disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer's risk allele, APOE-?4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-?4 being the major genetic risk factor for AD. PMID:25988319

  17. Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.

    PubMed Central

    Lee, J B; Farshy, C E; Hunter, E F; Hambie, E A; Wobig, G H; Larsen, S A

    1986-01-01

    Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis. PMID:3533984

  18. Endoscopic Repair of Frontal Sinus Cerebrospinal Fluid Leaks after Firearm Injuries: Report of Two Cases

    PubMed Central

    Reyes, Camilo; Solares, C. Arturo

    2015-01-01

    Objectives?To describe two cases of cerebrospinal fluid (CSF) leak repair after gunshot wound to the head. Design?Retrospective review of two cases. Settings?A large regional tertiary care facility. Participants?Two patients with gunshot wounds to the skull base. Main Outcome Measures?Preoperative and postoperative physical and radiologic findings. Results?Patients in this series underwent endoscopic surgery, debridement, and repair of CSF leaks after gunshot wounds to the head. To date, the patients are without CSF leak. Conclusions?Endoscopic closure of anterior skull base CSF leaks in patients with gunshot wounds can be safe and effective. Treatment should be decided by the severity of neurologic deterioration throughout the emergency period and the existence or absence of associated intracranial lesions. Timing for surgery should be decided with great care and with a multidisciplinary approach. PMID:26251818

  19. Determination of kynurenic acid in rat cerebrospinal fluid by HPLC with fluorescence detection.

    PubMed

    Bao, Ye; Luchetti, David; Schaeffer, Eric; Cutrone, Jingfang

    2016-01-01

    A sensitive HPLC method using fluorescence detection was developed to determine kynurenic acid (KYNA) level in rat cerebrospinal fluid (CSF). The method development was accomplished by screening different columns, optimizing zinc acetate concentration and determining the optimal HPLC flow rate. This method allowed direct injection of the CSF samples onto an Xselect C18 column and KYNA levels were measured fluorometrically by forming a fluorescent complex with zinc acetate that was delivered post-column. The limit of quantitation was 0.2 n m with 30 ?L injection, corresponding to 6 fmol (signal-to-noise ratio = 10). The improved sensitivity enabled the measurement of KYNA in naive and drug-treated rat CSF. Copyright © 2015 John Wiley & Sons, Ltd. PMID:25963282

  20. Quantification of Amino Acid Neurotransmitters in Cerebrospinal Fluid of Patients with Neurocysticercosis

    PubMed Central

    Camargo, José Augusto; Bertolucci, Paulo Henrique Ferreira

    2015-01-01

    Background : Neurocysticercosis is a parasitic disease that affects the central nervous system. Its main clinical manifestations are epileptic seizures. The objective of this study was to investigate the correlation between neurotransmitter concentrations in cerebrospinal fluid (CSF) and the different evolutive forms of neurocysticercosis with or without seizures. Methods : Neurotransmitter concentrations (Aspartate, Glutamate, GABA, Glutamine, Glycine, Taurine) were determined in CSF samples from 42 patients with neurocysticercosis divided into patients with the active cystic form (n = 24, 12 with and 12 without seizures) and patients with calcified form (n = 18, 12 with and 6 without seizures), and a control group consisting of 59 healthy subjects. Results : Alterations in amino acid concentration were observed in all patients with neurocysticercosis. Conclusion : We conclude that disturbances in amino acid metabolism accompany the presentation of neurocysticercosis. Replacement of the terms inactive cyst by reactive inactive cyst and calcification by reactive calcification is suggested. PMID:26157521

  1. Plasma oxytocin and vasopressin do not predict neuropeptide concentrations in human cerebrospinal fluid.

    PubMed

    Kagerbauer, S M; Martin, J; Schuster, T; Blobner, M; Kochs, E F; Landgraf, R

    2013-07-01

    The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinal fluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification. PMID:23574490

  2. Presence of morphine metabolites in human cerebrospinal fluid after intracerebroventricular administration of morphine.

    PubMed

    Sandouk, P; Serrie, A; Scherrmann, J M; Langlade, A; Bourre, J M

    1991-01-01

    After intracerebroventricular administration of morphine in four cancer patients, cerebrospinal fluid (CSF) was analyzed by two morphine radioimmunoassays (RIA), liquid chromatography (LC) and radioreceptor assay (RRA) to evaluate the presence of morphine metabolites. Immunoreactive morphine-like substances were detected by differential RIA's. The maximum concentrations of these compounds were achieved 3 hours after drug administration. These concentrations, according to the specificity of the antiserum, represent a mixture of several metabolites in which only morphine 3-glucuronide(M 3-G) and morphine 6-glucuronide (M 6-G) were identified by LC, and M 6-G by LC-RRA. These results confirm that brain is able to metabolize morphine to inactive (M 3-G) or more potent (M 6-G) derivatives. PMID:1820872

  3. The Choroid Plexus and Cerebrospinal Fluid: Emerging Roles in Development, Disease, and Therapy

    PubMed Central

    Bjornsson, Christopher S.; Dymecki, Susan M.; Gilbertson, Richard J.; Holtzman, David M.

    2013-01-01

    Although universally recognized as the source of cerebrospinal fluid (CSF), the choroid plexus (ChP) has been one of the most understudied tissues in neuroscience. The reasons for this are multiple and varied, including historical perceptions about passive and permissive roles for the ChP, experimental issues, and lack of clinical salience. However, recent work on the ChP and instructive signals in the CSF have sparked new hypotheses about how the ChP and CSF provide unexpected means for regulating nervous system structure and function in health and disease, as well as new ChP-based therapeutic approaches using pluripotent stem cell technology. This minisymposium combines new and established investigators to capture some of the newfound excitement surrounding the ChP-CSF system. PMID:24198345

  4. Spontaneous sphenoid sinus cerebrospinal fluid leak and meningoencephalocele – are they due to patent Sternberg's canal?

    PubMed Central

    Tomaszewska, Magdalena; Krzeski, Antoni

    2014-01-01

    Sternberg's canal is a congenital bony defect in the lateral wall of the sphenoid sinus. If it persists to adulthood, it may become a source of spontaneous cerebrospinal fluid leak (CSF) and meningoencephalocele. The aim of the study was to describe the authors’ experience and review articles related to spontaneous sphenoid sinus CSF leaks and Sternberg's canal. We analysed patients managed surgicallly due to sphenoid sinus CSF leak and performed a PubMed database search. Two female patients with spontaneous CSF leak of sphenoid origin were found. Both patients underwent surgery with the endoscopic endonasal approach, and the defect was closed using the multi-layer technique. Twelve articles related to CSF leaks of sphenoid origin (due to Sternberg's canal) were found in the PubMed database. Lines of lesser resistance within sphenoid bone may underlie CSF leak pathology together with intracranial hypertension. The endoscopic transnasal approach to the sphenoid sinus is an excellent alternative to standard transcranial procedures. PMID:26240642

  5. An integrated metabolomics approach for the research of new cerebrospinal fluid biomarkers of multiple sclerosis.

    PubMed

    Pieragostino, Damiana; D'Alessandro, Michele; di Ioia, Maria; Rossi, Claudia; Zucchelli, Mirco; Urbani, Andrea; Di Ilio, Carmine; Lugaresi, Alessandra; Sacchetta, Paolo; Del Boccio, Piero

    2015-06-01

    Multiple Sclerosis (MuS) is a disease caused due to an autoimmune attack against myelin components in which non proteic mediators may play a role. Recent research in metabolomics and lipidomics has been driven by rapid advances in technologies such as mass spectrometry and computational methods. They can be used to study multifactorial disorders like MuS, highlighting the effects of disease on metabolic profiling, regardless of the multiple trigger factors. We coupled MALDI-TOF-MS untargeted lipidomics and targeted LC-MS/MS analysis of acylcarnitines and aminoacids to compare cerebrospinal fluid metabolites in 13 MuS subjects and in 12 patients with Other Neurological Diseases (OND). After data processing and statistical evaluation, we found 10 metabolites that significantly (p < 0.05) segregate the two clinical groups. The most relevant result was the alteration of phospholipids levels in MuS and the correlation between some of them with clinical data. In particular lysophosphatidylcholines (m/z = 522.3 Da, 524.3 Da) and an unidentified peak at m/z = 523.0 Da correlated to the Link index, lysophosphatidylinositol (m/z = 573.3 Da) correlated to EDSS and phosphatidylinositol (m/z = 969.6 Da) correlated to disease duration. We also found high levels of glutamate in MuS. In conclusion, our integrated mass spectrometry approach showed high potentiality to find metabolic alteration in cerebrospinal fluid. These data, if confirmed in a wider clinical study, could open the door for the discovery of novel candidate biomarkers of MuS. PMID:25690641

  6. Attenuated antiaggregation effects of magnetite nanoparticles in cerebrospinal fluid of people with Alzheimer's disease.

    PubMed

    Gažová, Zuzana; Antošová, Andrea; Krištofiková, Zdena; Bartoš, Aleš; Rí?ný, Jan; Cechová, Linda; Klaschka, Jan; Rípová, Daniela

    2010-11-01

    It is well known that oligomeric/aggregated amyloid ? peptides are a key player in the pathogenesis of Alzheimer's disease and that different nanoparticles influence oligomerization/aggregation processes in experiments in vitro. Our previous results demonstrated antiaggregation effects of magnetite nanoparticles in the case of protein lysozyme, however, they have yet to be supported by biological samples containing peptides/proteins preaggregated in vivo. In the study, Thioflavin T based fluorescence was evaluated on cerebrospinal fluid samples from people with Alzheimer's disease/multiple sclerosis and corresponding age-related controls using magnetite nanoparticles incubated for 24 h. Our results are as follows: (i) fluorescence of samples without nanoparticles was significantly higher in both older groups (old controls and people with Alzheimer's disease) than in those of younger (young controls and people with multiple sclerosis), (ii) nanoparticles did not markedly influence a fluorescence intensity in young people but eliminated it in both old groups; nevertheless, the effects of nanoparticles were significantly lower in patients with Alzheimer's disease then in the age-matched controls, and finally (iii) significant positive correlation was observed between fluorescence of samples without nanoparticles and levels of phospho-tau. Our results support studies reporting enhanced aggregation of different peptides/proteins occurring during normal aging and demonstrate for the first time that peptides/proteins preaggregated in vivo during Alzheimer's disease are more resistant to the antiaggregation effects of magnetite nanoparticles than those of age-matched controls. A significant correlation with phospho-tau levels indicate that the in vitro test with magnetite nanoparticles and Thioflavin T dye on cerebrospinal fluid could be sensitive to changes mediated by early Alzheimer's disease stages. PMID:20721410

  7. Potential diagnostic applications of side chain oxysterols analysis in plasma and cerebrospinal fluid.

    PubMed

    Leoni, Valerio; Caccia, Claudio

    2013-07-01

    The neurospecific cholesterol 24-hydroxylase converts excess brain cholesterol into 24S-hydroxycholesterol (24OHC) which, via the liver X receptor (LXR), can increase the expression and synthesis of astrocyte ApoE. 24OHC effluxes directly from brain into plasma where it is considered an indicator of brain cholesterol turnover. It is reduced in neurodegenerative disease states proportionally to the severity of disease and the degree of brain atrophy. In the early phases of active disease, a higher rate of turnover may result in transitory increases in plasma 24OHC. Less than 1% of the total brain excretion of 24OHC occurs via the cerebrospinal fluid (CSF) whereas almost all 27-hydroxycholesterol (27OHC) excretion is dependent on the function of the blood-cerebrospinal fluid barrier. Iincreased CSF oxysterols were found in patients with neurodegenerative and neuroinflammatory diseases in the presence of barrier dysfunction. In neurodegeneration, free cholesterol released from dying cells may engulf neurons. Cholesterol also increases Amyloid ? (A?) deposition and tau pathology. ApoE, 24OHC, tau and soluble APP were correlated in Alzheimer disease (AD) samples. Excess of cholesterol converted into 24OHC may up-regulate ApoE synthesis which is a scavenger for A? and Tau. In AD this protective mechanism seems to be inefficient, probably due to the presence of high concentrations of 27OHC, microvascular dysfunction and the decreased efficiency of ApoE4 as lipid transporter and A? scavenger. 24OHC itself was cytotoxic. Analysis of side chain oxysterols in the CSF is likely to provided useful information about cholesterol metabolism and ApoE function in the pathogenesis of AD. PMID:23541982

  8. Cochlear and cerebrospinal fluid pressure: their inter-relationship and control mechanisms.

    PubMed

    Marchbanks, R J; Reid, A

    1990-06-01

    The patency of the cochlear aqueduct is a key factor in intra-cochlear hydromechanics. If patent, the cerebrospinal fluid (CSF) provides the reference pressure for the perilymph and also to a large extent the endolymph, since Reissner's membrane can only withstand a relatively small pressure differential. The aqueduct often becomes sealed as a natural process of ageing. In this instance the reference pressure is from a source, its position unknown, within the boundaries of the cochlea itself. Relatively large and rapid changes in the cerebrospinal fluid pressure may result from everyday events such as coughing (ca. 175 mm saline) and sneezing (ca. 250 mm saline). The resistive nature of the cochlear aqueduct and the mechanical compliance of the cochlear windows are probably important factors in limiting the amount of stress, and therefore possible damage, which may occur to the cochlea and cochlear windows for a given pressure change within the CSF system. A narrow aqueduct and compliant cochlear windows reduce the risk of structural damage. In practice, this should mean that the risk of structural damage will be increased by any process which reduces the compliance of one or both of the cochlear windows, for example, extremes of middle ear pressure perhaps brought about by Eustachian tube dysfunction or rapid barometric pressure changes. Techniques are now available which provide non-invasive indirect measures of perilymphatic pressure and CSF-perilymphatic pressure transfer. The tympanic membrane displacement measurement technique has been used to provide reliable measures of perilymphatic pressure and CSF-perilymphatic pressure transfer on an individual subject basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2194603

  9. miRNA contents of cerebrospinal fluid extracellular vesicles in glioblastoma patients

    PubMed Central

    Akers, Johnny C.; Ramakrishnan, Valya; Kim, Ryan; Phillips, Shirley; Kaimal, Vivek; Mao, Ying; Hua, Wei; Yang, Isaac; Fu, Chia-Chun; Nolan, John; Nakano, Ichiro; Yang, Yuanfan; Beaulieu, Martin; Carter, Bob S.; Chen, Clark C.

    2015-01-01

    Introduction Analysis of extracellular vesicles (EVs) derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of EVs in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in EVs derived from the serum and cerebrospinal fluid of glioblastoma patients. Methods EVs were isolated from glioblastoma cell lines as well as the plasma and CSF of glioblastoma patients. The microvesicle subpopulation was isolated by pelleting at 10,000×g for 30 min after cellular debris was cleared by a 2,000×g (20 min) spin. The exosome subpopulation was isolated by pelleting the microvesicle supernatant at 120,000×g (120 min). qRT-PCR was performed to examine the distribution of miR-21, miR-103, miR-24, and miR-125. Global miRNA profiling was performed in select glioblastoma CSF samples. Results In plasma and cell line derived EVs, the relative abundance of miRNAs in exosome and microvesicles were highly variable. In some specimens, the majority of the miRNA species were found in exosomes while in other, they were found in microvesicles. In contrast, CSF exosomes were enriched for miRNAs relative to CSF microvesicles. In CSF, there is an average of one molecule of miRNA per 150-25,000 EVs. Conclusion Most EVs derived from clinical biofluids are devoid of miRNA content. The relative distribution of miRNA species in plasma exosomes or microvesicles is unpredictable. In contrast, CSF exosomes are the major EV compartment that harbor miRNAs. PMID:25903655

  10. Creatine kinase isoenzyme BB concentrations in cerebrospinal fluid in asphyxiated preterm neonates.

    PubMed

    Talvik, T; Haldre, S; Sööt, A; Hämarik, M; Piirsoo, A; Mikelsaar, A V

    1995-10-01

    Creatine kinase isoenzyme BB was determined in cerebrospinal fluid (CSF) in 79 preterm neonates using an original enzyme-linked immunosorbent assay. The criterion for inclusion was an Apgar score of 7 or less at 5 min of life. Neurological examination was performed on day 2 and day 5 of life. CSF was obtained on the same days. Lumbar puncture was performed on 41 of these babies on day 2 and in 39 on day 5 of life (one baby underwent lumbar puncture twice). All babies had clinical features of hypoxic-ischemic encephalopathy (HIF) which was classified according to Sarnat and Sarnat. The control group consisted of 90 asphyxiated term babies and 30 adults without CNS pathology. The concentration of CK-BB in cerebrospinal fluid (mean +/- SD) was significantly higher (p < 0.0005) in preterm (168.0 +/- 2) than in term babies (29.0 +/- 3.1) and healthy adults (5.3 +/- 1.2). Our results demonstrate the possibility of using the classification system of Sarnat and Sarnat for assessment of the severity of brain damage not only in term, but also in preterm babies. Neonates with HIE stages II and III showed markedly higher CK-BB values than those with HIE I on day 2 (p < 0.025) and day 5 (p < 0.05) of life. CK-BB values were markedly higher in preterm babies with none of some primitive responses (head turning, Babkin's reflex, palmar grasp). The mean concentration of CK-BB was higher in neonates with retarded psychomotor development compared with those with normal development (p < 0.05) on day 3, and after 6 and 9 months. At 12 months of age no significant difference in median CK-BB concentration was detected between neonates with normal and developmental disturbances. PMID:8563233

  11. Commentary: Unnecessary preoperative epidural steroid injections lead to cerebrospinal fluid leaks confirmed during spinal stenosis surgery

    PubMed Central

    Epstein, Nancy E.

    2014-01-01

    Background: Increasingly, older patients with severe spinal stenosis/instability undergo multiple unnecessary preoperative epidural spinal injections (ESI), despite their risks and lack of long-term benefits. Here we add to the list of risks by showing how often preoperative ESI lead to punctate cerebrospinal fluid (CSF) fistulas documented during subsequent surgery (e.g. multilevel laminectomies with non-instrumented fusions). Methods: A series of 39 patients with spinal stenosis/instability prospectively underwent multilevel laminectomy/non-instrumented fusion utilizing lamina autograft and NanOss Bioactive. We asked how often preoperative ESI were performed in this population and how frequently they contributed to operatively confirmed punctate cerebrospinal fluid (CSF) fistulas. Notably, CSF leaks were clearly attributed to ESI, as they were located centrally/paracentrally at the L4-L5 level, just below hypertrophied/ossified yellow ligament (OYL), and were the exact size of a Tuohy needle with clean edges. Results: An average of 4.1 (range 2-12) preoperative ESI were performed in 33 of 39 patients undergoing average 4.3 level laminectomies and 1.3 level non-instrumented fusions; 6 (18.2%) patients exhibited operatively confirmed, punctate CSF fistulas attributed to these ESI. The most recent injections were administered between 2 and 5 weeks prior to surgery (average 3.9 weeks). Fistulas were primarily repaired with 7-0 GORE-TEX sutures and fibrin Sealant (Tisseel). Conclusions: Of 33 patients undergoing multilevel laminectomies with non-instrumented fusions receiving preoperative ESI, 6 (18.2%) had operatively confirmed punctate CSF fistulas due to preoperative ESI performed an average of 4.1 times per patient. PMID:25289153

  12. Cisterna magna microdialysis of sup 22 Na to evaluate ion transport and cerebrospinal fluid dynamics

    SciTech Connect

    Knuckey, N.W.; Fowler, A.G.; Johanson, C.E.; Nashold, J.R.; Epstein, M.H. )

    1991-06-01

    Microdialysis is used in vivo for measuring compounds in brain interstitial fluid. The authors describe another application of this technique to the central nervous system, namely microprobe dialysis in the cisterna magna to study the dynamics of ion transport and cerebrospinal fluid (CSF) formation in the rat. The choroid plexus is the major source of CSF, which is produced by active transport of Na from blood into the cerebral ventricles. Formation of CSF is directly proportional to the blood-to-CSF transport of Na. By injecting {sup 22}Na into the systemic circulation and quantifying its movement into CSF by microdialysis, one can reliably estimate alterations in the rate of CSF formation. The sensitivity of this system was determined by administering acetazolamide, a standard inhibitor of CSF production. Because acetazolamide is known to decrease CSF formation by 40% to 50%, the cisternal microdialysis system in animals treated with this drug should detect a corresponding decrease in the amount of {sup 22}Na dialyzed. This hypothesis is supported by the {sup 22}Na uptake curves for control versus treated animals: that is, by the acetazolamide-induced average diminution of about 45% in both the rate and extent of tracer accession to dialysate. Bumetanide, a loop diuretic, reduced by 30% the {sup 22}Na entry into dialysate. Microprobe dialysis of fluid in the cisterna magna is thus a minimally invasive and economical method for evaluating effects of drugs and hormones on the choroid plexus-CSF system.

  13. Effects of irregular cerebrospinal fluid production rate in human brain ventricular system

    NASA Astrophysics Data System (ADS)

    Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd

    2012-06-01

    Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

  14. Cryptococcus neoformans and Streptococcus pneumoniae co-infection in post-traumatic meningitis in a patient with unknown HIV status.

    PubMed

    Saleem, Faryal; Fasih, Naima; Zafar, Afia

    2015-10-01

    Meningitis is a serious disease associated with considerable morbidity and mortality. Mixed meningeal infections due to bacteria and fungi are exceptionally rare. Here we report a case of meningeal co-infection with cryptococcus neoformans and streptococcus pneumoniae in a patient with unknown human immunodeficiency virus status. Because of the rarity of such cases, stringent screening of every cerebrospinal fluid specimen to exclude the presence of multiple pathogens is imperative. Assessment of patients for immunodeficiencies in case of isolation of an opportunistic organism like cryptococcus is also needed. PMID:26440847

  15. Meningococcal Meningitis

    MedlinePLUS

    ... Fact sheets Features Commentaries 2014 Multimedia Contacts Meningococcal meningitis Fact sheet N°141 Updated November 2015 Key facts Meningococcal meningitis is a bacterial form of meningitis, a serious ...

  16. Flow induced by ependymal cilia dominates near-wall cerebrospinal fluid dynamics in the lateral ventricles

    PubMed Central

    Siyahhan, Bercan; Knobloch, Verena; de Zélicourt, Diane; Asgari, Mahdi; Schmid Daners, Marianne; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2014-01-01

    While there is growing experimental evidence that cerebrospinal fluid (CSF) flow induced by the beating of ependymal cilia is an important factor for neuronal guidance, the respective contribution of vascular pulsation-driven macroscale oscillatory CSF flow remains unclear. This work uses computational fluid dynamics to elucidate the interplay between macroscale and cilia-induced CSF flows and their relative impact on near-wall dynamics. Physiological macroscale CSF dynamics are simulated in the ventricular space using subject-specific anatomy, wall motion and choroid plexus pulsations derived from magnetic resonance imaging. Near-wall flow is quantified in two subdomains selected from the right lateral ventricle, for which dynamic boundary conditions are extracted from the macroscale simulations. When cilia are neglected, CSF pulsation leads to periodic flow reversals along the ventricular surface, resulting in close to zero time-averaged force on the ventricle wall. The cilia promote more aligned wall shear stresses that are on average two orders of magnitude larger compared with those produced by macroscopic pulsatile flow. These findings indicate that CSF flow-mediated neuronal guidance is likely to be dominated by the action of the ependymal cilia in the lateral ventricles, whereas CSF dynamics in the centre regions of the ventricles is driven predominantly by wall motion and choroid plexus pulsation. PMID:24621815

  17. Proteomics of Cerebrospinal Fluid: Throughput and Robustness Using a Scalable Automated Analysis Pipeline for Biomarker Discovery.

    PubMed

    Núñez Galindo, Antonio; Kussmann, Martin; Dayon, Loïc

    2015-11-01

    Cerebrospinal fluid (CSF) is a body fluid of high clinical relevance and an important source of potential biomarkers for brain-associated damages, such as traumatic brain injury and stroke, and for brain diseases, such as Alzheimer's and Parkinson's. Herein, we have implemented, evaluated, and validated a scalable automated proteomic pipeline (ASAP(2)) for the sample preparation and proteomic analysis of CSF, enabling increased throughput and robustness for biomarker discovery. Human CSF samples were depleted from abundant proteins and subjected to automated reduction, alkylation, protein digestion, tandem mass tag (TMT) 6-plex labeling, pooling, and sample cleanup in a 96-well-plate format before reversed-phase liquid chromatography tandem mass spectrometry (RP-LC MS/MS). We showed the impact on the CSF proteome coverage of applying the depletion of abundant proteins, which is usually performed on blood plasma or serum samples. Using ASAP(2) to analyze 96 identical CSF samples, we determined the analytical figures of merit of our shotgun proteomic approach regarding proteome coverage consistency (i.e., 387 proteins), quantitative accuracy, and individual protein variability. We demonstrated that, as for human plasma samples, ASAP(2) is efficient in analyzing large numbers of human CSF samples and is a valuable tool for biomarker discovery. The data has been deposited to the ProteomeXchange with identifier PXD003024. PMID:26452177

  18. Quantification of the cerebrospinal fluid from a new whole body MRI sequence

    NASA Astrophysics Data System (ADS)

    Lebret, Alain; Petit, Eric; Durning, Bruno; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe

    2012-03-01

    Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinal fluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.

  19. Cerebrospinal Rhinorrhea

    PubMed Central

    Calcaterra, Thomas C.; Moseley, John I.; Rand, Robert W.

    1977-01-01

    Cerebrospinal rhinorrhea is an uncommon complication of head trauma or of diverse types of intracranial diseases. Because of the risk of meningitis, this condition warrants immediate attention. If the leak fails to stop spontaneously in a short time, the precise site of the leak must be ascertained and surgical repair attempted. For the past 50 years craniotomy has been the principal operative approach; however, this method carries the risk of significant morbidity and protracted hospital stays, as well as a disappointing incidence of persistent leak. During the past decade extracranial operations for dural repair have been devised, and experience in the management of patients by a variety of such procedures illustrates the success of these operations. PMID:919524

  20. Bacterial meningitis caused by Veillonella parvula.

    PubMed

    Nukina, S; Hibi, A; Nishida, K

    1989-10-01

    A three-year-old girl injured her right eyelid with a toothbrush. The wound was sutured. Swelling of the eyelid, high fever and vomiting developed in spite of oral antibiotics for seven days. The findings of the cerebrospinal fluid (CSF) were white blood cells (WBC) 26,368/mm3 (90% polymorphs), protein 127 mg/dl, and sugar 0 mg/dl. Although Gram negative organisms were seen on the smear, aerobic culture was sterile. Later culture of CSF on admission grew anaerobic bacteria: Veillonella parvula. Intravenous administration of penicillins with cefotaxime (CTX), or of fosfomycin (FOM) were ineffective. Chloramphenicol (CP) cured the patient without neurological sequelae. There were no abnormal findings on brain CT scan. This is the first report of Veillonella meningitis. V. parvula appeared to have invaded the CSF from the abscess of the eyelid. It is necessary to consider anaerobic meningitis when there is a preceding pyogenic infection in the head. PMID:2515742

  1. The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

    PubMed

    Dowling, N Maritza; Johnson, Sterling C; Gleason, Carey E; Jagust, William J

    2015-01-15

    Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), ?-amyloid peptides 1-42 (A?(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau(181p) were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of A?(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/A?(1-42)-associated cognitive change across all brain regions examined. Significant direct effects of alterations in A?(1-42) levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus. Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudinal cognitive changes, suggesting that tau-related burden precedes neurometabolic dysfunction. While intriguing, the hypothesized mediational relationships require further validation. PMID:25450107

  2. A meta-analysis of serum and cerebrospinal fluid autoantibodies in neuropsychiatric systemic lupus erythematosus.

    PubMed

    Ho, Roger C; Thiaghu, C; Ong, Huiyi; Lu, Yanxia; Ho, Cyrus S; Tam, Wilson W; Zhang, Melvyn W

    2016-02-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most devastating presentations of SLE and comprises of psychiatric, central and peripheral neurological signs and symptoms. Previous studies suggest the possible associations between various autoantibodies (Abs) and NPSLE. The magnitudes of such association varied between studies. We performed a meta-analysis to pool data on serum and cerebrospinal fluid (CSF) levels and positivity of Abs in blood and cerebrospinal fluid in patients with NPSLE and SLE. A systematic literature search was conducted to identify studies that fulfilled inclusion criteria. A random-effects model was used to calculate overall combined odd ratio (OR) and mean levels with its corresponding 95% confidence interval to evaluate the relationship between individual Abs and NPSLE patients relative to SLE patients. Forty-one studies met the inclusion criteria and were used in this analysis. There was a significantly greater proportion of NPSLE patients who demonstrated positivity for serum anti-cardiolipin (aCL) Abs (OR=1.63, p=0.016), lupus anticoagulants (LA) Abs (OR=1.91 p=0.01), anti-phospholipid (APL) Abs (OR=2.08, p=0.001), anti-ribosomal P Abs (OR=2.29, p<0.001), anti-neuronal Abs (OR=9.50, p<0.001) as compared to SLE patients. In NPSLE patients, there was a significant increased prevalence of positive titres for CSF anti-neuronal Abs (OR=36.84, p=0.001) as compared to SLE patients. Among the 19 neuropsychiatric syndromes, the positivity of these serum autoantibodies were found specifically significantly associated with the manifestations of mood disorder, psychosis, cerebrovascular disease, seizure disorders, acute confusional state, cognitive dysfunction, headache, movement disorder, demyelinating syndrome and polyneuropathy, with ORs ranging from 1.84 to 4.73. Meta-regression identified proportion of women as significant moderator for the heterogeneity of aCL (p=0.004) and anti-neuronal Abs (p=0.0007); mean age for the heterogeneity of aCL (p=0.042) and LA (p=0.020) Abs, mean duration of illness for the heterogeneity of aCL Abs (p=0.035), and mean SLEDAI scores for the heterogeneity of anti-ribosomal P Abs (p=0.014). NPSLE patients are more likely to have elevated serum levels of aCL, LA, APL, anti-ribosomal P Abs and anti-neuronal Abs compared with SLE patients. Further research is required to evaluate the accuracy of using the above antibodies as an adjunct diagnostic tool in NPSLE. PMID:26497108

  3. Severe cochlear dysplasia causing recurrent meningitis: a surgical lesson.

    PubMed

    Stevenson, D S; Proops, D W; Phelps, P D

    1993-08-01

    Meningitis may be the sole presenting sign of a cerebrospinal fluid (CSF) fistula of the temporal bone. An eight-year-old boy suffering from recurrent meningitis was found to have bilateral severe cochlear dysplasia. Bilateral tympanotomies were performed, planning to obliterate each vestibule. In the right ear a stapedectomy was performed, resulting in a torrential 'CSF gusher' and difficulty in packing the vestibule. CSF rhinorrhoea requiring revision surgery and two episodes of gram-negative bacterial meningitis complicated the post-operative management, resulting in a prolonged hospital stay. Subsequently, the left ear was managed in a different fashion, leaving the stapes in situ, with grafts placed to seal the oval window niche. We would recommend this alternative procedure in cases of severe cochlear dysplasia, where abnormalities of the vestibule and basal turn of the cochlea mean that performing a stapedectomy to pack the vestibule may result in a severe 'CSF gusher', by opening directly into the subarachnoid space. PMID:8409727

  4. A differentially expressed set of microRNAs in cerebro-spinal fluid (CSF) can diagnose CNS malignancies.

    PubMed

    Drusco, Alessandra; Bottoni, Arianna; Laganà, Alessandro; Acunzo, Mario; Fassan, Matteo; Cascione, Luciano; Antenucci, Anna; Kumchala, Prasanthi; Vicentini, Caterina; Gardiman, Marina P; Alder, Hansjuerg; Carosi, Mariantonia A; Ammirati, Mario; Gherardi, Stefano; Luscrì, Marilena; Carapella, Carmine; Zanesi, Nicola; Croce, Carlo M

    2015-08-28

    Central Nervous System malignancies often require stereotactic biopsy or biopsy for differential diagnosis, and for tumor staging and grading. Furthermore, stereotactic biopsy can be non-diagnostic or underestimate grading. Hence, there is a compelling need of new diagnostic biomarkers to avoid such invasive procedures. Several biological markers have been proposed, but they can only identify specific prognostic subtype of Central Nervous System tumors, and none of them has found a standardized clinical application.The aim of the study was to identify a Cerebro-Spinal Fluid microRNA signature that could differentiate among Central Nervous System malignancies.CSF total RNA of 34 neoplastic and of 14 non-diseased patients was processed by NanoString. Comparison among groups (Normal, Benign, Glioblastoma, Medulloblastoma, Metastasis and Lymphoma) lead to the identification of a microRNA profile that was further confirmed by RT-PCR and in situ hybridization.Hsa-miR-451, -711, 935, -223 and -125b were significantly differentially expressed among the above mentioned groups, allowing us to draw an hypothetical diagnostic chart for Central Nervous System malignancies.This is the first study to employ the NanoString technique for Cerebro-Spinal Fluid microRNA profiling. In this article, we demonstrated that Cerebro-Spinal Fluid microRNA profiling mirrors Central Nervous System physiologic or pathologic conditions. Although more cases need to be tested, we identified a diagnostic Cerebro-Spinal Fluid microRNA signature with good perspectives for future diagnostic clinical applications. PMID:26246487

  5. Chemokine biomarkers in central nervous system tissue and cerebrospinal fluid in the Theiler's virus model mirror those in multiple sclerosis.

    PubMed

    Pachner, Andrew R; Li, Libin; Gilli, Francesca

    2015-12-01

    Chemokines have increasingly been implicated in inflammatory and infectious disease of the central nervous system, both as biomarkers and as molecules important in pathogenesis. Multiple sclerosis is a disabling disease of unknown etiology, and recently chemokines have been identified as being upregulated molecules in the disease. We were interested in how the chemokine expression patterns in the central nervous system of a viral model of multiple sclerosis, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), compared to that in humans with multiple sclerosis. Cerebrospinal fluid and spinal cord tissue were analyzed for expression of a range of cytokines and chemokines. Three chemokines, CXCL10, CXCL9, and CCL5 were strongly and specifically upregulated in both the cerebrospinal fluid and spinal cord in chronic disease, a pattern identical to that in multiple sclerosis. These data, the first study of cytokines in central nervous system tissue and cerebrospinal fluid in TMEV-IDD, support the hypothesis that multiple sclerosis is caused by chronic infection with an as-yet unidentified pathogen, possibly a picornavirus. PMID:26141421

  6. The body mass index (BMI) is significantly correlated with levels of cytokines and chemokines in cerebrospinal fluid.

    PubMed

    Larsson, Anders; Carlsson, Lena; Lind, Anne-Li; Gordh, Torsten; Bodolea, Constantin; Kamali-Moghaddam, Masood; Thulin, Måns

    2015-12-01

    Cytokines and chemokines regulate many functions in the body including the brain. The interactions between adipose tissue and the central nervous system (CNS) are important for the regulation of energy balance. CNS function is also influenced by age. The aim of the present study was to investigate the effects of body mass index (BMI) and age on cytokine and chemokine levels in cerebrospinal fluid. Cerebrospinal fluid samples (n=89) were collected from patients undergoing routine surgical procedures. The samples were analyzed using the multiplex proximity extension assay (PEA) in which 92 different cytokines are measured simultaneously using minute sample volume. We found no significant correlations between age and cytokine levels for any of the studied markers. In contrast, at a false discovery rate of 10%, 19 markers were significantly associated with BMI (in decreasing significance: FGF-5, ADA, Beta-NGF, CD40, IL-10RB, CCL19, TGF-alpha, SIRT2, TWEAK, SCF, CSF-1, 4E-BP1, DNER, LIF-R, STAMPB, CXCL10, CXCL6, VEGF-A and CX3CL1). This study reveals a clear effect of BMI on cytokine and chemokine levels in cerebrospinal fluid. PMID:26188367

  7. Elevated concentrations of neurofilament light chain in the cerebrospinal fluid of bipolar disorder patients.

    PubMed

    Jakobsson, Joel; Bjerke, Maria; Ekman, Carl Johan; Sellgren, Carl; Johansson, Anette G M; Zetterberg, Henrik; Blennow, Kaj; Landén, Mikael

    2014-09-01

    Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs. PMID:24694925

  8. Quantification of ?-Aminobutyric Acid in Cerebrospinal Fluid Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

    PubMed

    Arning, Erland; Bottiglieri, Teodoro

    2016-01-01

    We describe a simple stable isotope dilution method for accurate and precise measurement of ?-aminobutyric acid (GABA), a major inhibitory neurotransmitter in human cerebrospinal fluid (CSF) as a clinical diagnostic test. Determination of GABA in CSF (50 ?L) was performed utilizing high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Analysis of free and total GABA requires two individual sample preparations and mass spectrometry analyses. Free GABA in CSF is determined by a 1:2 dilution with internal standard (GABA-D2) and injected directly onto the HPLC-ESI-MS/MS system. Determination of total GABA in CSF requires additional sample preparation in order to hydrolyze all the bound GABA in the sample to the free form. This requires hydrolyzing the sample by boiling in acidic conditions (hydrochloric acid) for 4 h. The sample is then further diluted 1:10 with a 90 % acetonitrile/0.1 % formic acid solution and injected into the HPLC-ESI-MS/MS system. Each assay is quantified using a five-point standard curve and is linear from 6 nM to 1000 nM and 0.63 ?M to 80 ?M for free and total GABA, respectively. PMID:26602123

  9. Quantitation of 5-Methyltetrahydrofolate in Cerebrospinal Fluid Using Liquid Chromatography-Electrospray Tandem Mass Spectrometry.

    PubMed

    Arning, Erland; Bottiglieri, Teodoro

    2016-01-01

    We describe a simple stable isotope dilution method for accurate and precise measurement of cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF) as a clinical diagnostic test. 5-MTHF is the main biologically active form of folic acid and is involved in regulation of homocysteine and DNA synthesis. Measurement of 5-MTHF in CSF provides diagnostic information regarding diseases affecting folate metabolism within the central nervous system, in particular inborn errors of folate metabolism. Determination of 5-MTHF in CSF (50 ?L) was performed utilizing high performance liquid chromatography coupled with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). 5-MTHF in CSF is determined by a 1:2 dilution with internal standard (5-MTHF-(13)C5) and injected directly onto the HPLC-ESI-MS/MS system. Each assay is quantified using a five-point standard curve (25-400 nM) and has an analytical measurement range of 3-1000 nM. PMID:26602129

  10. Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

    PubMed Central

    Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.

    2013-01-01

    ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus. PMID:23781068

  11. Proteomic Analysis of Cerebrospinal Fluid in a Fulminant Case of Multiple Sclerosis

    PubMed Central

    Füvesi, Judit; Hanrieder, Jörg; Bencsik, Krisztina; Rajda, Cecilia; Kovács, S. Krisztián; Kaizer, László; Beniczky, Sándor; Vécsei, László; Bergquist, Jonas

    2012-01-01

    Multiple Sclerosis (MS) is a chronic disease, but in rare fulminant cases rapid progression may lead to death shortly after diagnosis. Currently there is no diagnostic test to predict disease course. The aim of this study was to identify potential biomarkers/proteins related to rapid progression. We present the case history of a 15-year-old male MS patient. Cerebrospinal fluid (CSF) was taken at diagnosis and at the time of rapid progression leading to the patient’s death. Using isobaric tag labeling and nanoflow liquid chromatography in conjunction with matrix assisted laser desorption/ionization time of flight tandem mass spectrometry we quantitatively analyzed the protein content of two CSF samples from the patient with fulminant MS as well as one relapsing-remitting (RR) MS patient and one control headache patient, whose CSF analysis was normal. Seventy-eight proteins were identified and seven proteins were found to be more abundant in both fulminant MS samples but not in the RR MS sample compared to the control. These proteins are involved in the immune response, blood coagulation, cell proliferation and cell adhesion. In conclusion, in this pilot study we were able to show differences in the CSF proteome of a rapidly progressing MS patient compared to a more typical clinical form of MS and a control subject. PMID:22837721

  12. Detection and analyses of ascorbyl radical in cerebrospinal fluid and serum of acute lymphoblastic leukemia.

    PubMed

    Nakagawa, K; Kanno, H; Miura, Y

    1997-12-01

    We have detected and analyzed a free radical in human cerebrospinal fluid (CSF) of acute lymphoblastic leukemia (ALL) for the first time using electron paramagnetic resonance (EPR) at ambient temperature. We have also introduced an alternative capillary method to measure the radical. EPR spectra of the radical show a characteristic doublet with hyperfine coupling value of 1.8 G and g = 2.005. Based on EPR measurements, computer simulation, and literature values, we have determined that the species is ascorbyl radical (AsR). The radical has been investigated in CSF samples from ALL patients having no therapy, undergoing chemotherapy, and following therapy. Determination of the ascorbyl radical concentrations in CSF and serum was attempted using known concentrations of a nitroxyl radical. In addition, comparison in CSF and serum for ALL has been made along with statistical analyses of the data obtained. We found that AsR in CSF and serum has a strong correlation in patients undergoing chemotherapy (n = 57, r = 0.57, P < 0.0001). Ascorbate in CSF and serum show good correlation in patients having therapy but not for patients after therapy. PMID:9398342

  13. Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation.

    PubMed

    Kooij, Gijs; Kopplin, Kathrin; Blasig, Rosel; Stuiver, Marchel; Koning, Nathalie; Goverse, Gera; van der Pol, Susanne M A; van Het Hof, Bert; Gollasch, Maik; Drexhage, Joost A R; Reijerkerk, Arie; Meij, Iwan C; Mebius, Reina; Willnow, Thomas E; Müller, Dominik; Blasig, Ingolf E; de Vries, Helga E

    2014-08-01

    Multiple sclerosis (MS) is a chronic neuro-inflammatory disorder, which is marked by the invasion of the central nervous system by monocyte-derived macrophages and autoreactive T cells across the brain vasculature. Data from experimental animal models recently implied that the passage of leukocytes across the brain vasculature is preceded by their traversal across the blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus. The correlation between the presence of leukocytes in the CSF of patients suffering from MS and the number of inflammatory lesions as detected by magnetic resonance imaging suggests that inflammation at the choroid plexus contributes to the disease, although in a yet unknown fashion. We here provide first insights into the involvement of the choroid plexus in the onset and severity of the disease and in particular address the role of the tight junction protein claudin-3 (CLDN3) in this process. Detailed analysis of human post-mortem brain tissue revealed a selective loss of CLDN3 at the choroid plexus in MS patients compared to control tissues. Importantly, mice that lack CLDN3 have an impaired BCSFB and experience a more rapid onset and exacerbated clinical signs of experimental autoimmune encephalomyelitis, which coincides with enhanced levels of infiltrated leukocytes in their CSF. Together, this study highlights a profound role for the choroid plexus in the pathogenesis of multiple sclerosis, and implies that CLDN3 may be regarded as a crucial and novel determinant of BCSFB integrity. PMID:24356983

  14. Super-Resolution Microscopy of Cerebrospinal Fluid Biomarkers as a Tool for Alzheimer's Disease Diagnostics.

    PubMed

    Zhang, William I; Antonios, Gregory; Rabano, Alberto; Bayer, Thomas A; Schneider, Anja; Rizzoli, Silvio O

    2015-01-01

    Alzheimer's disease (AD) is neuropathologically characterized by aggregates of amyloid-? peptides (A?) and tau proteins. The consensus in the AD field is that A? and tau should serve as diagnostic biomarkers for AD. However, their aggregates have been difficult to investigate by conventional fluorescence microscopy, since their size is below the diffraction limit (?200?nm). To solve this, we turned to a super-resolution imaging technique, stimulated emission depletion (STED) microscopy, which has a high enough precision to allow the discrimination of low- and high-molecular weight aggregates prepared in vitro. We used STED to analyze the structural organization of A? and tau in cerebrospinal fluid (CSF) from 36 AD patients, 11 patients with mild cognitive impairment (MCI), and 21 controls. We measured the numbers of aggregates in the CSF samples, and the aggregate sizes and intensities. These parameters enabled us to distinguish AD patients from controls with a specificity of ?87% and a sensitivity of ?79% . In addition, the aggregate parameters determined with STED microscopy correlated with the severity of cognitive impairment in AD patients. Finally, these parameters may be useful as predictive tools for MCI cases. The STED parameters of two MCI patients who developed AD during the course of the study, as well as of MCI patients whose A? ELISA values fall within the accepted range for AD, placed them close to the AD averages. We suggest that super-resolution imaging is a promising tool for AD diagnostics. PMID:25881910

  15. Partial characterization of a novel endogenous opioid in human cerebrospinal fluid

    SciTech Connect

    Miller, B.E.; Lipman, J.J.; Byrne, W.L.

    1987-12-07

    Human cerebrospinal fluid (CSF) contains many uncharacterized endogenous opioids, in addition to the known enkephalins, endorphins, and dynorphins. These opioids may be separated by gel filtration chromatography and identified by radioreceptor assay for opioid activity. One region of the chromatographic elution profile, designated Peak B has previously been shown to be related to the pain status of chronic pain patients. The authors now report that human Peak B isolated from the CSF of pain-free elective surgery patients is present at a typical concentration equivalent in activity to 1.4 pmol of morphine sulfate per ml of CSF measured by radioreceptor assay. At a dose of 0.06 and 0.12 pmol morphine sulfate equivalents of CSF (MSE), injected into the cerebroventricular system of the mouse, Peak B produced an antinociceptive effect, the intensity and duration of which was dose-dependent and which was antagonized by naloxone. The mouse vas deferens (MVD) preparation was inhibited by Peak B in a manner that was sensitive to antagonism by naloxone only at low (< 1.0 ..mu..M) but not at higher (>6.0 ..mu..M) concentrations of the antagonist. Peak B activity in the MVD assay was unaffected by treatment with trypsin or ..cap alpha..-chymotrypsin. 32 references, 4 figures, 1 table.

  16. Simultaneous Determination of All Forms of Biopterin and Neopterin in Cerebrospinal Fluid

    PubMed Central

    2014-01-01

    In humans, genetic defects of the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor in hydroxylation reactions, are associated with severe neurological disorders. The diagnosis of these conditions relies on the determination of BH4, dihydrobiopterin (BH2), and dihydroneopterin (NH2) in cerebrospinal fluid (CSF). As MS/MS is less sensitive than fluorescence detection (FD) for this purpose, the most widely used method since 1980 involves two HPLC runs including two differential off-line chemical oxidation procedures aiming to transform the reduced pterins into their fully oxidized fluorescent counterparts, biopterin (B) and neopterin (N). However, this tedious and time-consuming two-step indirect method underestimates BH4, BH2, and NH2 concentrations. Direct quantification of BH4 is essential for studying its metabolism and for monitoring the efficacy of BH4 supplementation in patients with genetic defects. Here we describe a single step method to simultaneously measure BH4, BH2, B, NH2, and N in CSF by HPLC coupled to FD after postcolumn coulometric oxidation. All target pterins were quantified in CSF with a small volume (100 ?L), and a single filtration step for sample preparation and analysis. As compared to the most widely used method in more than 100 CSF samples, this new assay is the easiest route for accurately determining in a single run BH4, BH2, and NH2 in CSF in deficit situations as well as for monitoring the efficacy of the treatment. PMID:24650440

  17. Plasma and cerebrospinal fluid pharmacokinetics of ABT-888 after oral administration in non-human primates

    PubMed Central

    Muscal, Jodi A.; Thompson, Patrick A.; Giranda, Vincent L.; Dayton, Brian D.; Bauch, Joy; Horton, Terzah; McGuffey, Leticia; Nuchtern, Jed G.; Dauser, Robert C.; Gibson, Brian W.; Blaney, Susan M.

    2010-01-01

    Purpose ABT-888 inhibits poly(ADP-ribose) polymerase (PARP) and may enhance the efficacy of chemotherapy and radiation in CNS tumors. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics (PK) of ABT-888 in a non-human primate (NHP) model that is highly predictive of human CSF penetration. Methods ABT-888, 5 mg/kg, was administered orally to three NHPs. Serial blood and CSF samples were obtained. Plasma and CSF concentrations of ABT-888 were measured using LC/MS/MS, and the resulting concentration versus time data were evaluated using non-compartmental and compartmental PK methods. Results The CSF penetration of ABT-888 was 57 ± 7% (mean ± SD). The peak ABT-888 concentration in the plasma was 0.62 ± 0.18 ?M. Plasma and CSF AUC0–? were 3.7 ± 1.7 and 2.1 ± 0.8 ?M h. PARP inhibition in peripheral blood mononuclear cells was evident 2 h after ABT-888 administration. Conclusion The CSF penetration of ABT-888 after oral administration was 57%. Plasma and CSF concentrations were in the range that has been shown to inhibit PARP activity in vivo in humans. PMID:19526240

  18. Cerebral blood flow and oxygen uptake, and cerebrospinal fluid biochemistry in severe coma 1

    PubMed Central

    Brodersen, Poul; Jørgensen, Erik O.

    1974-01-01

    Thirty-eight patients in coma due to head trauma, cerebrovascular accidents, hypoxia, hypoglycaemia, or barbiturate intoxication, and 15 cases of brain death were studied. Cerebral metabolic rate of oxygen (CMRO2) was obtained from the arteriovenous oxygen difference and cerebral blood flow (CBF) measured by intra-arterial 133Xenon method. If hypothermia and CNS depressants were excluded, CMRO2 below one-third of normal was incompatible with regaining of consciousness, but this was seen in only three comatose patients. Irrespective of the clinical outcome (death, vegetative survival, or recovery), CMRO2 values of one-third to two-thirds of normal were seen in the majority of coma patients. CMRO2 measurements were of no practical value to predict the prognosis in coma, even when the effect of temperature and sedatives were considered. In brain death the CBF studies gave indirect evidence of cerebral circulatory arrest. The cerebrospinal fluid (CSF) was obtained for analysis of lactate, pyruvate, and bicarbonate in 29 cases. Increased CSF lactate levels were found in all groups except barbiturate intoxication. The finding of a negative correlation between CSF bicarbonate and log CBF suggests that the CSFpH determines the wide range of CBF in coma. PMID:4838910

  19. Dosimetric model for antibody targeted radionuclide therapy of tumor cells in cerebrospinal fluid

    SciTech Connect

    Millar, W.T.; Barrett, A. )

    1990-02-01

    Although encouraging results have been obtained using systemic radioimmunotherapy in the treatment of cancer, it is likely that regional applications may prove more effective. One such strategy is the treatment of central nervous system leukemia in children by intrathecal instillation of targeting or nontargeting beta particle emitting radionuclide carriers. The beta particle dosimetry of the spine is assessed, assuming that the spinal cord and the cerebrospinal fluid compartment can be adequately represented by a cylindrical annulus. The radionuclides investigated were {sup 90}Y, {sup 131}I, {sup 67}Cu, and {sup 199}Au. It is shown that the radiation dose to the cord can be significantly reduced using short range beta particle emitters and that there is little advantage in using targeting carriers with these radionuclides. {sup 199}Au and {sup 67}Cu also have the advantage of having a suitable gamma emission for imaging, permitting pretherapy imaging and dosimetric calculations to be undertaken prior to therapy. If these methods prove successful, it may be possible to replace the external beam component used in the treatment of central nervous system leukemia in children by intrathecal radionuclide therapy, thus reducing or avoiding side effects such as growth and intellectual impairment.

  20. Analysis of Brain Nuclei Accessible to Ghrelin Present in the Cerebrospinal Fluid

    PubMed Central

    Cabral, Agustina; Fernandez, Gimena; Perello, Mario

    2013-01-01

    Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal trough the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner. PMID:24042041

  1. Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.

    PubMed

    Cabral, A; Fernandez, G; Perello, M

    2013-12-01

    Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal through the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild-type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner. PMID:24042041

  2. Systemic Pharmacokinetics and Cerebrospinal Fluid Uptake of Intravenous Ceftriaxone in Patients with Amyotrophic Lateral Sclerosis

    PubMed Central

    Zhao, Yanli; Cudkowicz, Merit E.; Shefner, Jeremy; Krivickas, Lisa; David, William S.; Vriesendorp, Francine; Pestronk, Alan; Caress, James B.; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Harmatz, Jerold S.; Schoenfeld, David; Greenblatt, David J

    2015-01-01

    The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS). The pharmacokinetics (PK) of ceftriaxone in plasma and cerebrospinal fluid (CSF) were investigated in 66 participants in a previously reported clinical trial. Their mean age was 51 years, and 65 % were male. Participants were randomly assigned to one of three treatment groups receiving intravenous infusions (mean duration: 25 minutes) every 12 hours of either: placebo and placebo; 2 grams ceftriaxone and placebo; or 2 grams ceftriaxone twice. Mean steady-state plasma PK variables were: volume of distribution, 14 liters (0.17 liters/kg); elimination half-life, 8 - 9 hours; total clearance, 17-21 mL/min (0.22 - 0.25 mL/min/kg). Values were not different between dosage groups. CSF PK analysis, determined through sparse CSF sampling, indicated apparent entry and elimination half-life values of 1.0 and 34 hours, respectively. With both dosage regimens, CSF concentrations were maintained above the target threshold of 1.0 ?M (0.55 ?g/mL) as determined from in vitro models. The plasma and CSF PK profile of ceftriaxone were used as a basis for planning the Phase 3 clinical trial of ceftriaxone in ALS. PMID:24771634

  3. Cerebrospinal fluid-based kinetic biomarkers of axonal transport in monitoring neurodegeneration.

    PubMed

    Fanara, Patrizia; Wong, Po-Yin A; Husted, Kristofor H; Liu, Shanshan; Liu, Victoria M; Kohlstaedt, Lori A; Riiff, Timothy; Protasio, Joan C; Boban, Drina; Killion, Salena; Killian, Maudi; Epling, Lorrie; Sinclair, Elisabeth; Peterson, Julia; Price, Richard W; Cabin, Deborah E; Nussbaum, Robert L; Brühmann, Jörg; Brandt, Roland; Christine, Chadwick W; Aminoff, Michael J; Hellerstein, Marc K

    2012-09-01

    Progress in neurodegenerative disease research is hampered by the lack of biomarkers of neuronal dysfunction. We here identified a class of cerebrospinal fluid-based (CSF-based) kinetic biomarkers that reflect altered neuronal transport of protein cargo, a common feature of neurodegeneration. After a pulse administration of heavy water (2H2O), distinct, newly synthesized 2H-labeled neuronal proteins were transported to nerve terminals and secreted, and then appeared in CSF. In 3 mouse models of neurodegeneration, distinct 2H-cargo proteins displayed delayed appearance and disappearance kinetics in the CSF, suggestive of aberrant transport kinetics. Microtubule-modulating pharmacotherapy normalized CSF-based kinetics of affected 2H-cargo proteins and ameliorated neurodegenerative symptoms in mice. After 2H2O labeling, similar neuronal transport deficits were observed in CSF of patients with Parkinson's disease (PD) compared with non-PD control subjects, which indicates that these biomarkers are translatable and relevant to human disease. Measurement of transport kinetics may provide a sensitive method to monitor progression of neurodegeneration and treatment effects. PMID:22922254

  4. Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease.

    PubMed

    Sweeney, Melanie D; Sagare, Abhay P; Zlokovic, Berislav V

    2015-07-01

    Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth muscle cells), glial cells (astrocytes and microglia), and neurons. Thus, identifying and integrating biomarkers of the NVU cell-specific responses and injury with established AD biomarkers, amyloid-? (A?) and tau, has a potential to contribute to better understanding of the disease process in dementias including AD. Here, we discuss the existing literature on cerebrospinal fluid biomarkers of the NVU cell-specific responses during early stages of dementia and AD. We suggest that the clinical usefulness of established AD biomarkers, A? and tau, could be further improved by developing an algorithm that will incorporate biomarkers of the NVU cell-specific responses and injury. Such biomarker algorithm could aid in early detection and intervention as well as identify novel treatment targets to delay disease onset, slow progression, and/or prevent AD. PMID:25899298

  5. Data for a comprehensive map and functional annotation of the human cerebrospinal fluid proteome

    PubMed Central

    Zhang, Yang; Guo, Zhengguang; Zou, Lili; Yang, Yehong; Zhang, Liwei; Ji, Nan; Shao, Chen; Wang, Yajie; Sun, Wei

    2015-01-01

    Knowledge about the normal human cerebrospinal fluid (CSF) proteome serves as a baseline reference for CSF biomarker discovery and provides insight into CSF physiology. In this study, high-pH reverse-phase liquid chromatography (hp-RPLC) was first integrated with a TripleTOF 5600 mass spectrometer to comprehensively profile the normal CSF proteome. A total of 49,836 unique peptides and 3256 non-redundant proteins were identified. To obtain high-confidence results, 2513 proteins with at least 2 unique peptides were further selected as bona fide CSF proteins. Nearly 30% of the identified CSF proteins have not been previously reported in the normal CSF proteome. More than 25% of the CSF proteins were components of CNS cell microenvironments, and network analyses indicated their roles in the pathogenesis of neurological diseases. The top canonical pathway in which the CSF proteins participated was axon guidance signaling. More than one-third of the CSF proteins (788 proteins) were related to neurological diseases, and these proteins constitute potential CSF biomarker candidates. The mapping results can be freely downloaded at http://122.70.220.102:8088/csf/, which can be used to navigate the CSF proteome. For more information about the data, please refer to the related original article [1], which has been recently accepted by Journal of Proteomics. PMID:26217727

  6. Reduced cerebrospinal fluid and plasma nerve growth factor in drug-naïve psychotic patients.

    PubMed

    Kale, Anvita; Joshi, Sadhana; Pillai, Anilkumar; Naphade, Nilesh; Raju, Msvk; Nasrallah, Henry; Mahadik, Sahebarao P

    2009-12-01

    Impaired expression and function of several major neurotrophic factors such as nerve growth factor (NGF) has been proposed to contribute to the neurodevelopmental pathology of schizophrenia. However, the evidence in the majority of studies is based on variable and inconsistent levels of plasma NGF in diverse populations of early psychosis or medicated patients with chronic schizophrenia. We report here the first study comparing NGF levels in cerebrospinal fluid (CSF) and plasma from a unique patient cohort (unmedicated, early psychotic patients with similar racial and dietary patterns) and matched healthy controls. Significantly lower levels of NGF in both CSF (p=0.038) and plasma (p=0.002) were observed in drug-naïve first-episode psychosis patients as compared to controls. The levels of NGF in the CSF correlated (p=0.05) to the plasma values in controls. The data on plasma NGF confirm the reported deficits of NGF in drug-naïve first-episode psychosis. The reduced levels first time observed here may have important implications to repeatedly reported neurobiological and clinical deficits which are discussed. PMID:19713082

  7. Cerebrospinal Fluid Cytology of Lyme Neuroborreliosis: A Report of 3 Cases with Literature Review.

    PubMed

    Xing, Juan; Radkay, Lisa; Monaco, Sara E; Roth, Christine G; Pantanowitz, Liron

    2015-10-01

    Lyme disease can affect the central nervous system causing a B-cell-predominant lymphocytic pleocytosis. Since most reactions to infection in the cerebrospinal fluid (CSF) are typically T-cell predominant, a B-cell-predominant lymphocytosis raises concern for lymphoma. We present 3 Lyme neuroborreliosis cases in order to illustrate the challenging cytomorphological and immunophenotypic features of their CSF specimens. Three male patients who presented with central nervous system manifestations were diagnosed with Lyme disease. The clinical presentation, laboratory tests, CSF cytological examination and flow-cytometric studies were described for each case. CSF cytology showed lymphocytic pleocytosis with increased plasmacytoid cells and/or plasma cells. Flow cytometry showed the presence of polytypic B lymphocytes with evidence of plasmacytic differentiation in 2 cases. In all cases, Lyme disease was confirmed by the Lyme screening test and Western blotting. In such cases of Lyme neuroborreliosis, flow cytometry of CSF samples employing plasmacytic markers and cytoplasmic light-chain analysis is diagnostically helpful to exclude lymphoma. PMID:26343489

  8. Cerebrospinal fluid-iophendylate contrast on gradient-echo MR images.

    PubMed

    Jack, C R; Gehring, D G; Ehman, R L; Felmlee, J P

    1988-11-01

    The effect on the signal intensities of cerebrospinal fluid (CSF) and iophendylate (Pantopaque) and on CSF-iophendylate contrast was studied in vitro with a small-nutation-angle (alpha) gradient refocused magnetic resonance (MR) imaging technique (GRASS) as alpha, repetition time (TR), and echo time (TE) were varied. CSF signal intensity was consistently greater than that of iophendylate. Therefore, retained intraspinal iophendylate may be considered in the differential diagnosis of focal areas of low signal intensity at the periphery of the spinal canal on GRASS images. At constant TE and TR, an increase in alpha from 6 degrees to 45 degrees increased the signal intensities of CSF and iophendylate but decreased CSF-iophendylate contrast. At constant alpha and TR, an increase in TE from 13 to 28 msec decreased the signal intensities of CSF and iophendylate but increased contrast. At constant alpha and TE, an increase in TR from 50 to 400 msec increased the signal intensities of CSF and iophendylate, as well as contrast. Clinical examples of the contrast behavior of retained intraspinal iophendylate on both spin-echo and GRASS images corroborate the experimental findings. Retained intraspinal iophendylate may mimic the appearance of intra-or extra-dural lesions, magnetic susceptibility artifact, and flow on gradient-echo MR images of the spine. PMID:3175007

  9. Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease.

    PubMed

    Gui, Ya Xing; Liu, Hai; Zhang, Li Shan; Lv, Wen; Hu, Xing Yue

    2015-11-10

    The differential diagnosis of Parkinson's diseases (PD) is challenging, especially in the early stages of the disease. We developed a microRNA profiling strategy for exosomal miRNAs isolated from cerebrospinal fluid (CSF) in PD and AD. Sixteen exosomal miRNAs were up regulated and 11 miRNAs were under regulated significantly in PD CSF when compared with those in healthy controls (relative fold > 2, p < 0.05). MiR-1 and miR-19b-3p were validated and significantly reduced in independent samples. While miR-153, miR-409-3p, miR-10a-5p, and let-7g-3p were significantly over expressed in PD CSF exosome. Bioinformatic analysis by DIANA-mirPath demonstrated that Neurotrophin signaling, mTOR signaling, Ubiquitin mediated proteolysis, Dopaminergic synapse, and Glutamatergic synapse were the most prominent pathways enriched in quantiles with PD miRNA patterns. Messenger RNA (mRNA) transcripts [amyloid precursor protein (APP), ?-synuclein (?-syn), Tau, neurofilament light gene (NF-L), DJ-1/PARK7, Fractalkine and Neurosin] and long non-coding RNAs (RP11-462G22.1 and PCA3) were differentially expressed in CSF exosomes in PD and AD patients. These data demonstrated that CSF exosomal RNA molecules are reliable biomarkers with fair robustness in regard to specificity and sensitivity in differentiating PD from healthy and diseased (AD) controls. PMID:26497684

  10. Cerebrospinal fluid biomarkers of neurovascular dysfunction in mild dementia and Alzheimer's disease

    PubMed Central

    Sweeney, Melanie D; Sagare, Abhay P; Zlokovic, Berislav V

    2015-01-01

    Alzheimer's disease (AD) is the most common form of age-related dementias. In addition to genetics, environment, and lifestyle, growing evidence supports vascular contributions to dementias including dementia because of AD. Alzheimer's disease affects multiple cell types within the neurovascular unit (NVU), including brain vascular cells (endothelial cells, pericytes, and vascular smooth muscle cells), glial cells (astrocytes and microglia), and neurons. Thus, identifying and integrating biomarkers of the NVU cell-specific responses and injury with established AD biomarkers, amyloid-? (A?) and tau, has a potential to contribute to better understanding of the disease process in dementias including AD. Here, we discuss the existing literature on cerebrospinal fluid biomarkers of the NVU cell-specific responses during early stages of dementia and AD. We suggest that the clinical usefulness of established AD biomarkers, A? and tau, could be further improved by developing an algorithm that will incorporate biomarkers of the NVU cell-specific responses and injury. Such biomarker algorithm could aid in early detection and intervention as well as identify novel treatment targets to delay disease onset, slow progression, and/or prevent AD. PMID:25899298

  11. The predictive value of cerebrospinal fluid tap-test in normal pressure hydrocephalus.

    PubMed

    Damasceno, B P; Carelli, E F; Honorato, D C; Facure, J J

    1997-06-01

    Eighteen patients (mean age of 66.5 years) with normal pressure hydrocephalus (NPH) underwent a ventriculo-peritoneal shunt surgery. Prior to operation a cerebrospinal fluid tap-test (CSF-TT) was performed with measurements of gait pattern and psychometric functions (memory, visuo-motor speed and visuo-constructive skills) before and after the removal of 50 ml CSF by lumbar puncture (LP). Fifteen patients improved and 3 were unchanged after surgery. Short duration of disease, gait disturbance preceding mental deterioration, wide temporal horns and small sulci on CT-scan were associated with good outcome after shunting. There was a good correlation between the results of CSF-TT and shunt surgery (chi 2 = 4.11, phi = 0.48, p < 0.05), with gait test showing highest correlation (r = 0.99, p = 0.01). In conclusion, this version of CSF-TT proved to be an effective test to predict improvement after shunting in patients with NPH. PMID:9629375

  12. ID3 contributes to cerebrospinal fluid seeding and poor prognosis in medulloblastoma

    PubMed Central

    2013-01-01

    Background The inhibitor of differentiation (ID) genes have been implicated as promoters of tumor progression and metastasis in many human cancers. The current study investigated the expression and functional roles of ID genes in seeding and prognosis of medulloblastoma. Methods ID gene expression was screened in human medulloblastoma tissues. Knockdown of ID3 gene was performed in medulloblastoma cells in vitro. The expression of metastasis-related genes after ID3 knockdown was assessed. The effect of ID3 knockdown on tumor seeding was observed in an animal model in vivo. The survival of medulloblastoma patients was plotted according to the ID3 expression levels. Results Significantly higher ID3 expression was observed in medulloblastoma with cerebrospinal fluid seeding than tumors without seeding. Knockdown of ID3 decreased proliferation, increased apoptosis, and suppressed the migration of D283 medulloblastoma cells in vitro. In a seeding model of medulloblastoma, ID3 knockdown in vivo with shRNA inhibited the growth of primary tumors, prevented the development of leptomeningeal seeding, and prolonged animal survival. High ID3 expression was associated with shorter survival of medulloblastoma patients, especially in Group 4 medulloblastomas. Conclusions High ID3 expression is associated with medullolbastoma seeding and is a poor prognostic factor, especially in patients with Group 4 tumors. ID3 may represent the metastatic/ aggressive phenotype of a subgroup of medulloblastoma. PMID:23768125

  13. Inductively coupled microfluidic pressure meter for in vivo monitoring of cerebrospinal fluid shunt function.

    PubMed

    Song, S-H; Gillies, G T; Begley, M R; Utz, M; Broaddus, W C

    2012-04-01

    A microfluidic pressure sensor with inductively coupled, wireless readout capability has been developed for integration into cerebrospinal fluid shunt valve implants. The sensor consists of a deformable PDMS film that is bonded over a microfluidic reservoir, forming a fluidic capacitor. Deflection of the capacitor membrane is detected remotely through a shift in the resonance frequency of a micro-fabricated LC circuit. Sensors were fabricated by a combination of conventional MEMS technologies and rapid soft lithography. A direct pattern transfer technique was used to pattern the deformable PDMS film with a metal coating for the capacitive readout. The mechanical response of the fluidic capacitor was characterized by measuring the deflection of the PDMS film using an extrinsic Fabry-Perot interferometer (EFPI), and wireless sensing was demonstrated by the shift in resonance frequency of the sensor via an inductively coupled antenna. The sensor transduces pressure into a change in resonant frequency with sensitivity >?3.4?ppm Pa?¹ and responsivity 4.6?kHz Pa?¹, over a dynamic range of 0~3 kPa. PMID:22316101

  14. Evidence for Fungal Infection in Cerebrospinal Fluid and Brain Tissue from Patients with Amyotrophic Lateral Sclerosis

    PubMed Central

    Alonso, Ruth; Pisa, Diana; Marina, Ana Isabel; Morato, Esperanza; Rábano, Alberto; Rodal, Izaskun; Carrasco, Luis

    2015-01-01

    Among neurogenerative diseases, amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by a progressive motor neuron dysfunction in the motor cortex, brainstem and spinal cord. ALS is the most common form of motor neuron disease; yet, to date, the exact etiology of ALS remains unknown. In the present work, we have explored the possibility of fungal infection in cerebrospinal fluid (CSF) and in brain tissue from ALS patients. Fungal antigens, as well as DNA from several fungi, were detected in CSF from ALS patients. Additionally, examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients. PMID:25892962

  15. Leptin Levels Are Negatively Correlated with 2-Arachidonoylglycerol in the Cerebrospinal Fluid of Patients with Osteoarthritis

    PubMed Central

    Nicholson, James; Azim, Syed; Rebecchi, Mario J.; Galbavy, William; Feng, Tian; Reinsel, Ruth; Rizwan, Sabeen; Fowler, Christopher J.; Benveniste, Helene; Kaczocha, Martin

    2015-01-01

    Background There is compelling evidence in humans that peripheral endocannabinoid signaling is disrupted in obesity. However, little is known about the corresponding central signaling. Here, we have investigated the relationship between gender, leptin, body mass index (BMI) and levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the serum and cerebrospinal fluid (CSF) of primarily overweight to obese patients with osteoarthritis. Methodology/Principal Findings Patients (20 females, 15 males, age range 44-78 years, BMI range 24-42) undergoing total knee arthroplasty for end-stage osteoarthritis were recruited for the study. Endocannabinoids were quantified by liquid chromatography – mass spectrometry. AEA and 2-AG levels in the serum and CSF did not correlate with either age or BMI. However, 2-AG levels in the CSF, but not serum, correlated negatively with CSF leptin levels (Spearman’s ? -0.48, P=0.0076, n=30). No such correlations were observed for AEA and leptin. Conclusions/Significance In the patient sample investigated, there is a negative association between 2-AG and leptin levels in the CSF. This is consistent with pre-clinical studies in animals, demonstrating that leptin controls the levels of hypothalamic endocannabinoids that regulate feeding behavior. PMID:25835291

  16. Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

    PubMed Central

    2011-01-01

    Background Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear. Findings We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture. CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters. Conclusions Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment. PMID:22029888

  17. Approach to Cerebrospinal Fluid (CSF) Biomarker Discovery and Evaluation in HIV Infection

    SciTech Connect

    Price, Richard W.; Peterson, Julia; Fuchs, Dietmar; Angel, Thomas E.; Zetterberg, Henrik; Hagberg, Lars; Spudich, Serena S.; Smith, Richard D.; Jacobs, Jon M.; Brown, Joseph N.; Gisslen, Magnus

    2013-12-13

    Central nervous system (CNS) infection is a nearly universal facet of systemic HIV infection that varies in character and neurological consequences. While clinical staging and neuropsychological test performance have been helpful in evaluating patients, cerebrospinal fluid (CSF) biomarkers present a valuable and objective approach to more accurate diagnosis, assessment of treatment effects and understanding of evolving pathobiology. We review some lessons from our recent experience with CSF biomarker studies. We have used two approaches to biomarker analysis: targeted, hypothesis-driven and non-targeted exploratory discovery methods. We illustrate the first with data from a cross-sectional study of defined subject groups across the spectrum of systemic and CNS disease progression and the second with a longitudinal study of the CSF proteome in subjects initiating antiretroviral treatment. Both approaches can be useful and, indeed, complementary. The first is helpful in assessing known or hypothesized biomarkers while the second can identify novel biomarkers and point to broad interactions in pathogenesis. Common to both is the need for well-defined samples and subjects that span a spectrum of biological activity and biomarker concentrations. Previouslydefined guide biomarkers of CNS infection, inflammation and neural injury are useful in categorizing samples for analysis and providing critical biological context for biomarker discovery studies. CSF biomarkers represent an underutilized but valuable approach to understanding the interactions of HIV and the CNS and to more objective diagnosis and assessment of disease activity. Both hypothesis-based and discovery methods can be useful in advancing the definition and use of these biomarkers.

  18. Incidence of Pinhole Type Durotomy and Subsequent Cerebrospinal Fluid Leakage Following Simple Laminectomy

    PubMed Central

    Bawany, Faizan Imran; Emaduddin, Muhammad; Hussain, Mehwish; Yousuful Islam, Mohammad; Khan, Muhammad Shahzeb

    2015-01-01

    Study Design Cross sectional study. Purpose The purpose of this study was to determine the incidence and the associated risk factors of pinhole type of durotomy and cerebrospinal fluid (CSF) leakage following a simple laminectomy for spinal stenosis. Overview of Literature The incidence of spinal stenosis is expected to rise with increasing life expectancy. Moreover, lumbar spinal stenosis is the most common indication for spinal injury in the geriatric population. It is therefore important to identify and prevent the risks associated with laminectomy, the most widely used surgical procedure for spinal stenosis. The serious complication of incidental dural tear or durotomy and subsequent CSF leakage has not been studied in the region of Southeast Asia. Methods In this cross sectional study, we included 138 adult patients (age>18 years), who underwent a simple laminectomy for lumbar stenosis between 2011 and 2012. CSF leakage was the main outcome variable. Patients' wounds were examined for CSF leakage up to 1 week postoperatively. Results The incidence of pinhole type durotomy and subsequent CSF leakage in our region was 8.7%. Univariate analysis showed that hypertension, diabetes and smoking were significantly associated with durotomy and increased CSF leakage by 16.72, 44.25, and 33.71 times, respectively. Multivariate analysis showed that only smoking and diabetes significantly increased the chances of leakage. Conclusions Glycemic control and cessation of smoking prior to a simple laminectomy procedure reduced the incidence of a dural tear. Larger clinical studies on this lethal complication are required. PMID:26240710

  19. Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

    PubMed Central

    2012-01-01

    There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects. In the present review, we explore the mechanisms involved in the behavioral and physiological effects of ?-endorphin (?-END), especially those involving the cerebrospinal fluid (CSF), as a message transport system to reach distant brain areas. The major source of ?-END are the pro-opio-melano-cortin (POMC) neurons, located in the arcuate hypothalamic nucleus (ARH), bordering the 3rd ventricle. In addition, numerous varicose ?-END-immunoreactive fibers are situated close to the ventricular surfaces. In the present paper we surveyed the evidence that volume transmission via the CSF can be considered as an option for messages to reach remote brain areas. Some of the points discussed in the present review are: release mechanisms of ?-END, independence of peripheral versus central levels, central ?-END migration over considerable distances, behavioral effects of ?-END depend on location of ventricular administration, and abundance of mu and delta opioid receptors in the periventricular regions of the brain. PMID:22883598

  20. Mechanism for measurement of flow rate of cerebrospinal fluid in hydrocephalus shunts.

    PubMed

    Rajasekaran, Sathish; Kovar, Spencer; Qu, Peng; Inwald, David; Williams, Evan; Qu, Hongwei; Zakalik, Karol

    2014-01-01

    The measurement of the flow rate of cerebrospinal fluid (CSF) or existence of CSF flow inside the shunt tube after shunt implant have been reported as tedious process for both patients and doctors; this paper outlines a potential in vitro flow rate measurement method for CSF in the hydrocephalus shunt. The use of implantable titanium elements in the shunt has been proposed to allow for an accurate temperature measurement along the shunt for prediction of CSF flow rate. The CSF flow velocity can be deduced by decoupling the thermal transfer in the measured differential time at a pair of measurement spots of the titanium elements. Finite element analyses on the fluidic and thermal behaviors of the shunt system have been conducted. Preliminary bench-top measurements on a simulated system have been carried out. The measured flow rates, ranging from 0.5 mm/sec to 1.0 mm/sec, which is clinically practical, demonstrate good agreements with the simulation results. PMID:25570411

  1. Measurement of fluorescent probes concentration ratio in the cerebrospinal fluid for early detection of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Harbater, Osnat; Gannot, Israel

    2014-03-01

    The pathogenic process of Alzheimer's Disease (AD), characterized by amyloid plaques and neurofibrillary tangles in the brain, begins years before the clinical diagnosis. Here, we suggest a novel method which may detect AD up to nine years earlier than current exams, minimally invasive, with minimal risk, pain and side effects. The method is based on previous reports which relate the concentrations of biomarkers in the Cerebrospinal Fluid (CSF) (A? and Tau proteins) to the future development of AD in mild cognitive impairment patients. Our method, which uses fluorescence measurements of the relative concentrations of the CSF biomarkers, replaces the lumbar puncture process required for CSF drawing. The process uses a miniature needle coupled trough an optical fiber to a laser source and a detector. The laser radiation excites fluorescent probes which were prior injected and bond to the CSF biomarkers. Using the ratio between the fluorescence intensities emitted from the two biomarkers, which is correlated to their concentration ratio, the patient's risk of developing AD is estimated. A theoretical model was developed and validated using Monte Carlo simulations, demonstrating the relation between fluorescence emission and biomarker concentration. The method was tested using multi-layered tissue phantoms simulating the epidural fat, the CSF in the sub-arachnoid space and the bone. These phantoms were prepared with different scattering and absorption coefficients, thicknesses and fluorescence concentrations in order to simulate variations in human anatomy and in the needle location. The theoretical and in-vitro results are compared and the method's accuracy is discussed.

  2. Tau and Amyloid-? Cerebrospinal Fluid Biomarkers have Differential Relationships with Cognition in Mild Cognitive Impairment.

    PubMed

    Malpas, Charles B; Saling, Michael M; Velakoulis, Dennis; Desmond, Patricia; O'Brien, Terence J

    2015-01-01

    Alzheimer's disease (AD) is characterized by two primary pathologies: tau-related neurofibrillary tangles and the extracellular accumulation of amyloid-? (A?). The development of these pathologies is topologically distinct early in the disease, with A? beginning to accumulate as a diffuse, neocortical pathology, while tau-related pathology begins to form in mesial temporal regions. This study investigated the hypothesis that, by virtue of this distinction, there exist preferential associations between the primary pathologies and aspects of the cognitive phenotype. We investigated the relationship between cerebrospinal fluid (CSF) biomarkers for tau and A? pathologies with neurocognitive measures in 191 patients with mild cognitive impairment (MCI). Participants completed cognitive tests of new learning, information processing speed, and working memory. Separate regression models were computed and then followed up with mediation analyses to examine the predictive status of CSF biomarkers. The effect of A? on learning was mediated by phospho-tau (p?=?0.008). In contrast, A? had a direct effect on information processing speed that was not mediated by phospho-tau (p?=?0.59). No predictors were significant for working memory. This study provided evidence for a differential relationship of A? and phospho-tau pathologies on the neurocognitive phenotype of MCI. This supports the proposition that these primary AD pathologies maximally affect different aspects of cognition, and has potential implications for cognitive assessments and the use of biomarkers in disease-modifyingtherapeutic trials. PMID:26401775

  3. Zinc in Alzheimer's Disease: A Meta-Analysis of Serum, Plasma, and Cerebrospinal Fluid Studies.

    PubMed

    Ventriglia, Mariacarla; Brewer, George J; Simonelli, Ilaria; Mariani, Stefania; Siotto, Mariacristina; Bucossi, Serena; Squitti, Rosanna

    2015-01-01

    To evaluate whether zinc levels in serum, plasma, and cerebrospinal fluid are altered in Alzheimer's disease (AD), we performed meta-analyses of 27 studies on the topic published from 1983 to 2014. The subjects' sample obtained by merging studies was a pooled total of 777 AD subjects and 1,728 controls for serum zinc studies, 287 AD subjects and 166 controls for plasma zinc, and of 292 AD subjects and 179 controls for CSF zinc. The main result of this meta-analysis is the very high heterogeneity among the studies either in demographic terms or in methodological approaches. Although we considered these effects in our analyses, the heterogeneity persisted and it has to be taken into account in the interpretation of the results. Our meta-analysis indicated that serum zinc appears significantly decreased in AD patients compared with healthy controls, and this result is confirmed when serum and plasma studies were analyzed together. If we considered the age-matched studies, the meta-analysis carried out on only six studies showed no significant difference in zinc levels between AD and healthy controls (SMD?=-0.55, 95% CI (-1.18; 0.09); p?=?0.094; I2?=?91%). In the light of these findings, we speculated about the possibility that the decreases observed could indicate a possible dietary zinc deficiency and we suggested that the possible involvement of zinc alterations in AD may have an interplay with copper metabolism. PMID:25697706

  4. Structure and functions of human cerebrospinal fluid lipoproteins from individuals of different APOE genotypes.

    PubMed

    Rebeck, G W; Alonzo, N C; Berezovska, O; Harr, S D; Knowles, R B; Growdon, J H; Hyman, B T; Mendez, A J

    1998-01-01

    Recent data have implicated apolipoprotein E (apoE) in neuritic outgrowth, synaptic stability, and Alzheimer's disease; these data led us to examine the normal role of apoE-containing lipoproteins in the central nervous system (CNS). We isolated lipoproteins from human cerebrospinal fluid (CSF) in order to examine their composition and potential functions. CSF particles were composed of approximately one-third protein, one-third phospholipid, and one-third cholesterol. ApoE3 formed homodimers and heterodimers with apoA-II, while apoE4, as expected, was monomeric. We addressed the function of CSF lipoproteins with assays of cholesterol efflux and cholesterol influx. CSF lipoproteins decreased intracellular levels of cholesterol in cholesterol-loaded fibroblasts, suggesting these particles can act to remove excess lipids from cells. CSF lipoproteins competed for 125I-labeled LDL degradation by fibroblasts, suggesting they can also interact with the LDL receptor. Furthermore, CSF lipoproteins labeled with the fluorescent dye Dil were internalized by neuroglioma cells and primary neurons and astrocytes in culture. Together, these data support a model of CSF lipoproteins acting to remove lipids from degenerating cells and delivering lipids to cells for new membrane synthesis or storage. PMID:9454626

  5. Identification of a Biomarker in Cerebrospinal Fluid for Neuronopathic Forms of Gaucher Disease

    PubMed Central

    Zigdon, Hila; Savidor, Alon; Levin, Yishai; Meshcheriakova, Anna; Schiffmann, Raphael; Futerman, Anthony H.

    2015-01-01

    Gaucher disease, a recessive inherited metabolic disorder caused by defects in the gene encoding glucosylceramidase (GlcCerase), can be divided into three subtypes according to the appearance of symptoms associated with central nervous system involvement. We now identify a protein, glycoprotein non-metastatic B (GPNMB), that acts as an authentic marker of brain pathology in neurological forms of Gaucher disease. Using three independent techniques, including quantitative global proteomic analysis of cerebrospinal fluid (CSF) in samples from Gaucher disease patients that display neurological symptoms, we demonstrate a correlation between the severity of symptoms and GPNMB levels. Moreover, GPNMB levels in the CSF correlate with disease severity in a mouse model of Gaucher disease. GPNMB was also elevated in brain samples from patients with type 2 and 3 Gaucher disease. Our data suggest that GPNMB can be used as a marker to quantify neuropathology in Gaucher disease patients and as a marker of treatment efficacy once suitable treatments towards the neurological symptoms of Gaucher disease become available. PMID:25775479

  6. Endoscopic Contralateral Superiorly Based Mucoperiosteal Nasal Septal Flap for Closure of Cerebrospinal Fluid Leak

    PubMed Central

    Eviatar, Ephraim; Gavriel, Haim

    2013-01-01

    Objective A novel local contralateral superiorly based mucoperiosteal nasal septal flap (CSBMNSF) for closure of a cerebrospinal fluid (CSF) leak from the middle anterior base of the skull is described. Materials and Methods A retrospective review of patients having endoscopic sinus surgery (ESS) with a CSF leak between 2000 and 2009 was performed. The surgical technique is described. Two vertical parallel incisions are performed anteriorly and posteriorly in the contralateral septal mucosa, joined inferiorly by a horizontal incision. Elevation of the flap is completed, leaving it pedicled superiorly. A window is created at the highest aspect of the nasal septum to allow transfer of the flap to the affected side. Results Four patients with a CSF leak post-ESS for excision of a congenital meningocele, tumor removal, and chronic sinusitis are described. All were treated successfully using a CSBMNSF. Conclusion A novel, easy-to-handle local flap for closure of defects in the anterior middle skull base is described. The use of this flap offers less morbidity and less bulkiness compared with other local or regional flaps. PMID:24436901

  7. Changes in Purines Concentration in the Cerebrospinal Fluid of Pregnant Women Experiencing Pain During Active Labor.

    PubMed

    Schmidt, André P; Böhmer, Ana E; Hansel, Gisele; Soares, Félix A; Oses, Jean P; Giordani, Alex T; Posso, Irimar P; Auler, José Otávio C; Mendes, Florentino F; Félix, Elaine A; Portela, Luís V; Souza, Diogo O

    2015-11-01

    Labor pain has been reported as a severe pain and can be considered as a model of acute visceral pain. It is well known that extracellular purines have an important role in pain signaling in the central nervous system. This study analyzes the relationship between extracellular purines and pain perception during active labor. A prospective observational study was performed. Cerebrospinal fluid (CSF) levels of the purines and their metabolites were compared between women at term pregnancy with labor pain (n = 49) and without labor pain (Caesarian section; n = 47). Control groups (healthy men and women without chronic or acute pain-n = 40 and 32, respectively) were also investigated. The CSF levels of adenosine were significantly lower in the labor pain group (P = 0.026) and negatively correlated with pain intensity measured by a visual analogue scale (r = -0.48, P = 0.0005). Interestingly, CSF levels of uric acid were significantly higher in healthy men as compared to women. Additionally, pregnant women showed increased CSF levels of ADP, GDP, adenosine and guanosine and reduced CSF levels of AMP, GTP, and uric acid as compared to non-pregnant women (P < 0.05). These findings suggest that purines, in special the nucleoside adenosine, are associated with pregnancy and labor pain. PMID:26408294

  8. Application of polymerase chain reaction on cerebrospinal fluid for diagnosis of cerebral coenurosis in small ruminants.

    PubMed

    Oryan, Ahmad; Amrabadi, Omidreza; Sharifiyazdi, Hassan; Moazeni, Mohammad; Akbari, Maryam; Ghane, Mohsen

    2015-10-01

    Sheep and goats serve as intermediate hosts for the canine tapeworm Taenia multiceps. The cysts produced by the intermediate stage of parasite are usually found in the cerebral hemispheres of small ruminants, and the resulting disease is commonly known as coenurosis. Coenurosis is clinically manifested in the form of various nervous symptoms, depending on the exact location of the cyst. The variety of neurological symptoms contributes to the complexity of clinical diagnosis and reinforces the need for a more specific and acceptable diagnostic approach. We demonstrated here, for the first time, that the T. multiceps DNA is present in the cerebrospinal fluid (CSF) of the infected sheep and goats. In addition, the molecular genetic marker of the mitochondrial DNA was applied phylogenetically to show that our isolates together with other T. multiceps strains comprised a monophyletic group that is a sister to Taenia krabbei. Pairwise comparison between the cox1 sequences of our study and other T. multiceps genotypes existing in the GenBank showed similarity ranging from 98 to 100%. Accordingly, the polymerase chain reaction (PCR) can be used for amplification of DNA of the parasite originated from the CSF and provides a valuable method for accurate identification of coenurosis cases. PMID:26122997

  9. Ultrasound-guided atlanto-occipital puncture for cerebrospinal fluid analysis on the standing horse.

    PubMed

    Depecker, M; Bizon-Mercier, C; Couroucé-Malblanc, A

    2014-01-11

    The atlanto-occipital site (AO) is convenient for retrieving an adequate volume and quality of cerebrospinal fluid (CSF) in the diagnosis of neurological disease in horses. However, general anaesthesia is not always possible for horses displaying severe neurological signs, or for economical reasons. The objectives of the present work were to determine the feasibility and safety of ultrasound-guided CSF puncture at the AO site on the standing horse. Seven horses (six healthy and one mildly ataxic) were sedated with acepromazine (0.02 mg/kg bodyweight intravenously or 0.04 mg/kg bodyweight intramuscularly) and detomidine (0.01 mg/kg bodyweight intravenously), and placed in stocks or in a recovery stall with the head kept on a headstand. Puncture was performed by ultrasonographic guidance with a parasagittal technique, as previously described, using a 20 g, 3.5 inch spinal needle. In all horses, no adverse reaction was observed when crossing the dura mater and 20 ml of CSF was rapidly retrieved without any blood contamination. Ultrasound-guided CSF puncture can be performed easily at the AO site on a healthy standing horse. Regarding the potential risk of this procedure, safety measures and close observation are essential. Further studies on a larger amount of ataxic horses are also required before considering this technique as an alternative option for CSF puncture. PMID:24225443

  10. In Vivo Imaging of Lymphatic Drainage of Cerebrospinal Fluid in Mouse

    PubMed Central

    2013-01-01

    Background Mouse models are commonly used to study central nervous system disorders, in which cerebrospinal fluid (CSF) drainage may be disturbed. However, mouse CSF drainage into lymphatics has not been thoroughly characterized. We aimed to image this using an in vivo approach that combined quantum dot fluorescent nanoparticles with hyperspectral imaging. Findings Quantum dot 655 was injected into the CSF of the cisterna magna in seven mice and visualized by in vivo hyperspectral imaging at time points 20 and 40 min, 1, 2, and 6 h after injection. In controls (n?=?4), quantum dots were applied directly onto intact dura mater covering the cisterna magna. After imaging, lymph nodes in the neck were harvested and processed post-mortem for histological analysis. After injection into the CSF, quantum dot signal was detected in vivo in submandibular lymph nodes of all mice studied as early as 20 min, but not in controls. Post-mortem gross and histological examination of lymph nodes confirmed in vivo observations. Conclusions Non-invasive in vivo hyperspectral imaging is a useful tool to study CSF lymphatic drainage and is relevant to understanding this pathway in CNS disease models. PMID:24360130

  11. Hippocampal glucose metabolism is associated with cerebrospinal fluid estrogen levels in postmenopausal women with Alzheimer's disease.

    PubMed

    Schönknecht, Peter; Henze, Marcus; Hunt, Aoife; Klinga, Klaus; Haberkorn, Uwe; Schröder, Johannes

    2003-10-30

    Animal studies indicate that estrogens, such as 17beta-estradiol (E(2)), may enhance hippocampal metabolism and function. In postmenopausal Alzheimer's disease (AD) patients, cerebrospinal fluid (CSF) E(2) levels were significantly lower than in non-demented controls. This finding was inversely correlated with CSF beta-amyloid levels. To address the potential impact of this finding, E(2) levels in CSF were correlated with regional cerebral [18F]2-fluoro-2-deoxy-D-glucose (FDG) uptake as measured using positron emission tomography (PET) in six postmenopausal AD patients. CSF E(2) levels were determined using an electro-chemiluminescence-immunoassay on the Roche Elecsys 2010 immunoassay analyzer. Basic image processing was done by MEDx, using SPM routines for spatial normalization and statistics. CSF E(2) levels were significantly correlated with cerebral glucose metabolism in the left hippocampus. This is the first clinical study indicating an association between CSF E(2) concentration and hippocampal glucose metabolism in postmenopausal women with AD. PMID:14561431

  12. Targeted human cerebrospinal fluid proteomics for the validation of multiple Alzheimer’s disease biomarker candidates

    PubMed Central

    Choi, Yong Seok; Hou, Shuyu; Choe, Leila H.; Lee, Kelvin H.

    2013-01-01

    There is significant interest in the development of methods to validate novel biomarkers for Alzheimer’s disease (AD) diagnosis. Previously, a proteomic panel of cerebrospinal fluid (CSF) biomarker candidates that differentiated AD and non-AD CSF with accuracy higher than 90% was found; information about these CSF proteins can be used to develop multiple reaction monitoring (MRM) based analytical assays, which offer the possibility of quantifying protein expression level changes in samples, as well as, validation among multiple laboratories. Here we report an MRM assay that demonstrates good linearity (average R2 = 0.969) and reproducibility (average coefficient of variance of 6.93%) for the proposed AD CSF biomarkers. MRM quantification results of A?1-40, A?1-42, retinol-binding protein and cystatin C correlated well with those from ELISA (average R2 = 0.974). Analysis shows that 12 out of 16 selected targets exhibit the same trend in protein expression as that in literature. PMID:23735279

  13. Distinguishing the cerebrospinal fluid cytokine profile in neuropsychiatric systemic lupus erythematosus from other autoimmune neurological diseases.

    PubMed

    Ichinose, Kunihiro; Arima, Kazuhiko; Ushigusa, Takeshi; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Horai, Yoshiro; Nakajima, Hideki; Kawashiri, Shin-Ya; Iwamoto, Naoki; Tamai, Mami; Nakamura, Hideki; Origuchi, Tomoki; Motomura, Masakatsu; Kawakami, Atsushi

    2015-04-01

    Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication in SLE. Although the mechanism of NPSLE remains unclear, cytokines and chemokines are considered to be involved in their pathogenesis. Here we used Bio-Plex Pro assays to examine 27 types of cytokines and chemokines in the cerebrospinal fluid (CSF) of 32 NPSLE patients. We used the CSF of 20 patients with multiple sclerosis (MS) and 22 patients with neuromyelitis optica (NMO) as a disease control group. Fourteen of 27 cytokines/chemokines were significantly higher in the NPSLE patients compared to the MS/NMO patients. We could identify six "minimum predictive markers" by using a weighted-voting algorithm that could distinguish NPSLE from MS and NMO: interleukin (IL)-17, IL-2, interferon (IFN)-?, IL-5, basic fibroblast growth factor (FGF)-basic and IL-15. The determination of various types of CSF cytokine profiles may contribute to the diagnosis of NPSLE and may help elucidate the mechanisms underlying this disease. PMID:25656641

  14. Quantitative Analysis of Cerebrospinal Fluid Pressure Gradients in Healthy Volunteers and Patients with Normal Pressure Hydrocephalus

    PubMed Central

    HAYASHI, Naokazu; MATSUMAE, Mitsunori; YATSUSHIRO, Satoshi; HIRAYAMA, Akihiro; ABDULLAH, Afnizanfaizal; KURODA, Kagayaki

    2015-01-01

    Magnetic resonance imaging (MRI) can depict not only anatomical information, but also physiological factors such as velocity and pressure gradient. Measurement of these physiological factors is necessary to understand the cerebrospinal fluid (CSF) environment. In this study we quantified CSF motion in various parts of the CSF space, determined changes in the CSF environment with aging, and compared CSF pressure gradient between patients with idiopathic normal pressure hydrocephalus (iNPH) and healthy elderly volunteers. Fifty-seven healthy volunteers and six iNPH patients underwent four-dimensional (4D) phase-contrast (PC) MRI. CSF motion was observed and the pressure gradient of CSF was quantified in the CSF space. In healthy volunteers, inhomogeneous CSF motion was observed whereby the pressure gradient markedly increased in the center of the skull and gradually decreased in the periphery of the skull. For example, the pressure gradient at the ventral surface of the brainstem was 6.6 times greater than that at the convexity of the cerebrum. The pressure gradient was statistically unchanged with aging. The pressure gradient of patients with iNPH was 3.2 times greater than that of healthy volunteers. The quantitative analysis of 4D-PC MRI data revealed that the pressure gradient of CSF can be used to understand the CSF environment, which is not sufficiently given by subjective impression of the anatomical image. PMID:26226976

  15. Zebrafish cerebrospinal fluid mediates cell survival through a retinoid signaling pathway.

    PubMed

    Chang, Jessica T; Lehtinen, Maria K; Sive, Hazel

    2016-01-01

    Cerebrospinal fluid (CSF) includes conserved factors whose function is largely unexplored. To assess the role of CSF during embryonic development, CSF was repeatedly drained from embryonic zebrafish brain ventricles soon after their inflation. Removal of CSF increased cell death in the diencephalon, indicating a survival function. Factors within the CSF are required for neuroepithelial cell survival as injected mouse CSF but not artificial CSF could prevent cell death after CSF depletion. Mass spectrometry analysis of the CSF identified retinol binding protein 4 (Rbp4), which transports retinol, the precursor to retinoic acid (RA). Consistent with a role for Rbp4 in cell survival, inhibition of Rbp4 or RA synthesis increased neuroepithelial cell death. Conversely, ventricle injection of exogenous human RBP4 plus retinol, or RA alone prevented cell death after CSF depletion. Zebrafish rbp4 is highly expressed in the yolk syncytial layer, suggesting Rbp4 protein and retinol/RA precursors can be transported into the CSF from the yolk. In accord with this suggestion, injection of human RBP4 protein into the yolk prevents neuroepithelial cell death in rbp4 loss-of-function embryos. Together, these data support the model that Rbp4 and RA precursors are present within the CSF and used for synthesis of RA, which promotes embryonic neuroepithelial survival. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 75-92, 2016. PMID:25980532

  16. Association of cerebrospinal fluid A?42 with A2M gene in cognitively normal subjects

    PubMed Central

    Millard, Steven P.; Lutz, Franziska; Li, Ge; Galasko, Douglas R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby; Yu, Chang-En; Peskind, Elaine R.; Bekris, Lynn M.

    2013-01-01

    Low cerebrospinal fluid (CSF) A?42 levels correlate with increased brain A? deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of A? from the brain. In addition, APOE ?4 carriers have lower CSF A?42 levels than non-carriers. The hypothesis of this investigation was that CSF A?42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of A? from the brain. CSF A?42 levels were tested for associations with A? degradation and clearance genes and APOE ?4. Twenty-four SNPs located within the 5? and 3? regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF A?42 levels were associated with APOE ?4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF A?42 levels in controls, but not in AD patients, even after adjusting for APOE ?4. These results suggest that genetic variation within the A2M gene influences CSF A?42 levels. PMID:24011543

  17. Role of cerebrospinal fluid biomarkers in clinical trials for Alzheimer's disease modifying therapies.

    PubMed

    Kang, Ju-Hee; Ryoo, Na-Young; Shin, Dong Wun; Trojanowski, John Q; Shaw, Leslie M

    2014-12-01

    Until now, a disease-modifying therapy (DMT) that has an ability to slow or arrest Alzheimer's disease (AD) progression has not been developed, and all clinical trials involving AD patients enrolled by clinical assessment alone also have not been successful. Given the growing consensus that the DMT is likely to require treatment initiation well before full-blown dementia emerges, the early detection of AD will provide opportunities to successfully identify new drugs that slow the course of AD pathology. Recent advances in early detection of AD and prediction of progression of the disease using various biomarkers, including cerebrospinal fluid (CSF) A?1-42, total tau and p-tau181 levels, and imagining biomarkers, are now being actively integrated into the designs of AD clinical trials. In terms of therapeutic mechanisms, monitoring these markers may be helpful for go/no-go decision making as well as surrogate markers for disease severity or progression. Furthermore, CSF biomarkers can be used as a tool to enrich patients for clinical trials with prospect of increasing statistical power and reducing costs in drug development. However, the standardization of technical aspects of analysis of these biomarkers is an essential prerequisite to the clinical uses. To accomplish this, global efforts are underway to standardize CSF biomarker measurements and a quality control program supported by the Alzheimer's Association. The current review summarizes therapeutic targets of developing drugs in AD pathophysiology, and provides the most recent advances in the. PMID:25598657

  18. Diagnosis of acute leukemia in cerebrospinal fluid (CSF-acute leukemia).

    PubMed

    Crespo-Solis, Erick; López-Karpovitch, Xavier; Higuera, Jesús; Vega-Ramos, Beatriz

    2012-10-01

    Cerebrospinal fluid-acute leukemia (CSF-acute leukemia) is a frequent and serious complication in patients with acute leukemia. One of the major problems of this complication is the diagnosis process itself. CSF cytology is currently considered the gold standard for establishing the diagnosis, a technique which presents various processing limitations, seriously impacting the predictive values. In the last 11 years, studies of CSF flow cytometry analysis done in patients with acute leukemia have demonstrated superiority in comparison with CSF cytology. Although comparative studies between these two techniques have been reported since 2001, no new consensus or formal changes to the gold standard have been established for the CSF acute leukemia diagnosis. The evidence suggests that positive flow cytometry cases, considered as indeterminate cases, will behave like disease in the central nervous system (CNS). Nevertheless, we think there are some variables and considerations that must be first evaluated under research protocols before CNS relapse can be established with only one positive flow cytometry analysis in the setting of indeterminate CSF samples. This paper proposes a diagnostic algorithm and complementary strategies. PMID:22639108

  19. Clinical utility of cerebrospinal fluid biomarkers in the diagnosis of early Alzheimer’s disease

    PubMed Central

    Blennow, Kaj; Dubois, Bruno; Fagan, Anne M.; Lewczuk, Piotr; de Leon, Mony J.; Hampel, Harald

    2015-01-01

    Several potential disease-modifying drugs for Alzheimer’s disease (AD) have failed to show any effect on disease progression in clinical trials, conceivably because the AD subjects are already too advanced to derive clinical benefit from treatment and because diagnosis based on clinical criteria alone introduces a high misdiagnosis rate. Thus, well-validated biomarkers for early detection and accurate diagnosis are crucial. Low cerebrospinal fluid (CSF) concentrations of the amyloid-? (A?1-42) peptide, in combination with high total tau and phosphorylated tau, are sensitive and specific biomarkers highly predictive of progression to AD dementia in patients with mild cognitive impairment. However, interlaboratory variations in the results seen with currently available immunoassays are of concern. Recent worldwide standardization efforts and quality control programs include standard operating procedures for both preanalytical (e.g., lumbar puncture and sample handling) and analytical (e.g., preparation of calibration curve) procedures. Efforts are also ongoing to develop highly reproducible assays on fully automated instruments. These global standardization and harmonization measures will provide the basis for the generalized international application of CSF bio-markers for both clinical trials and routine clinical diagnosis of AD. PMID:24795085

  20. Analysis of cerebrospinal fluid ?-aminobutyric acid by capillary electrophoresis with laser-induced fluorescence detection.

    PubMed

    Casado, Mercedes; Molero, Marta; Sierra, Cristina; García-Cazorla, Angels; Ormazabal, Aida; Artuch, Rafael

    2014-04-01

    The measurement of ?-aminobutyric acid (GABA) is suitable for investigating various neurological disorders. In this study, a sensitive and selective method for free GABA quantification in cerebrospinal fluid (CSF) has been standardised. This method is based on CE with LIF detection using 4-fluoro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-F) as a derivatisating agent. The reaction conditions (NBD-F concentration, pH, temperature and reaction time) and the electrophoretic parameters (run buffer composition and pH and separation voltage) were optimised to obtain the maximum derivatisation efficiency and electrophoretic resolution. The best resolution was obtained using 200 mM sodium borate, 10 mM SDS, 8.5 mM ?-CD, pH 10 and 20 kV voltage. The method was linear in the concentration range of 2.5-1000 nM with good inter- and intra-assay precision values. The effects of CSF handling on free GABA concentrations were also evaluated. Our results show that the time delay between CSF collection and freezing strongly increases the CSF GABA values. Age-related reference values were established in 55 paediatric controls. The influence of antiepileptic therapy on free CSF GABA was studied in 38 neuropaediatric patients. Significantly, higher GABA values were obtained in patients taking valproic acid or vigabatrin therapy, which are antiepileptic drugs that modulate GABA metabolism. PMID:24338894

  1. Cerebrospinal Fluid Metabolome in Mood Disorders-Remission State has a Unique Metabolic Profile

    PubMed Central

    Kaddurah-Daouk, Rima; Yuan, Peixiong; Boyle, Stephen H.; Matson, Wayne; Wang, Zhi; Zeng, Zhao Bang; Zhu, Hongjie; Dougherty, George G.; Yao, Jeffrey K.; Chen, Guang; Guitart, Xavier; Carlson, Paul J.; Neumeister, Alexander; Zarate, Carlos; Krishnan, Ranga R.; Manji, Husseini K.; Drevets, Wayne

    2012-01-01

    Targeted metabolomics provides an approach to quantify metabolites involved in specific molecular pathways. We applied an electrochemistry-based, targeted metabolomics platform to define changes in tryptophan, tyrosine, purine and related pathways in the depressed and remitted phases of major depressive disorder (MDD). Biochemical profiles in the cerebrospinal fluid of unmedicated depressed (n = 14; dMDD) or remitted MDD subjects (n = 14; rMDD) were compared against those in healthy controls (n = 18; HC). The rMDD group showed differences in tryptophan and tyrosine metabolism relative to the other groups. The rMDD group also had higher methionine levels and larger methionine-to-glutathione ratios than the other groups, implicating methylation and oxidative stress pathways. The dMDD sample showed nonsignificant differences in the same direction in several of the metabolic branches assessed. The reductions in metabolites associated with tryptophan and tyrosine pathways in rMDD may relate to the vulnerability this population shows for developing depressive symptoms under tryptophan or catecholamine depletion. PMID:22993692

  2. Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.

    PubMed

    Karch, André; Hermann, Peter; Ponto, Claudia; Schmitz, Matthias; Arora, Amandeep; Zafar, Saima; Llorens, Franc; Müller-Heine, Annika; Zerr, Inga

    2015-05-01

    The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p < 0.001), MV (p = 0.004), and VV (p = 0.001) genotype. Receiver operating characteristic analyses showed values of area under the curve of 0.76-0.80 for the different genotypes indicating a good diagnostic validity of the test. Total tau can be used as a diagnostic test for the assessment of prion protein type when codon 129 genotype is known. It provides valuable information for physicians and next of kin about the further course of disease. PMID:25749129

  3. Meta-analysis of apolipoprotein E levels in the cerebrospinal fluid of patients with Alzheimer's disease.

    PubMed

    Talwar, Puneet; Sinha, Juhi; Grover, Sandeep; Agarwal, Rachna; Kushwaha, Suman; Srivastava, M V Padma; Kukreti, Ritushree

    2016-01-15

    The possible association between Apolipoprotein E (ApoE) levels in the cerebrospinal fluid (CSF) and Alzheimer's disease (AD) has been studied extensively. However, previous findings have been inconsistent. We conducted a meta-analysis of observational studies, seeking to provide insights into ApoE's potential as a biomarker for AD. A systematic literature search of PubMed (MEDLINE), EMBASE, and Web of Science was performed to retrieve relevant studies evaluating ApoE levels in CSF from AD subjects and controls. The association between ApoE levels in the CSF and AD was estimated by the weighted mean difference (WMD) and 95% confidence interval (CI) using a random-effect model. We identified 24 studies that included 1064AD cases and 1338 non-demented controls. Although the pooled WMD did not indicate a significant association between AD and ApoE levels (-0.30mg/l; 95% CI: -0.69 to 0.09; P=0.13), sub-group analysis controlling for patient sample size (n?43) revealed significantly lower ApoE levels (WMD: -0.66mg/l; 95% CI: -1.02 to -0.31; P=0.0002) among patients with AD than in controls. Publication bias was absent and sensitivity analysis did not result in any significant change in the pooled estimates, indicating highly stable results. The present meta-analysis indicates the potential of CSF ApoE levels as a predictor of AD association. PMID:26723997

  4. A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

    PubMed

    Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

    2015-11-01

    In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. PMID:26247808

  5. A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces

    PubMed Central

    Buishas, Joel; Gould, Ian G.; Linninger, Andreas A.

    2014-01-01

    Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 µL per mOsm in the ventricle and by 0.835 µL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema. PMID:25358881

  6. Management of Meningitis Caused by Multi Drug-Resistant Acinetobacter Baumannii: Clinical, Microbiological and Pharmacokinetic Results in a Patient Treated with Colistin Methanesulfonate

    PubMed Central

    Schiaroli, Elisabetta; Pasticci, Maria Bruna; Cassetta, Maria Iris; Fallani, Stefania; Castrioto, Corrado; Pirro, Matteo; Novelli, Andrea; De Angelis, Lucia Henrici; D’Andrea, Marco Maria; Mezzatesta, Maria Lina; Baldelli, Franco; Mencacci, Antonella

    2015-01-01

    This paper reports on a 71- year-old Caucasian male who underwent neurosurgery for an oligodendroglioma, followed by a cranial-sinus fistula and cerebrospinal fluid rhinorrhea. The clinical course was complicated due to an extensively drug-resistant Acinetobacter baumannii meningitis. The patient was treated with colistin methanesulfonate, intrathecal for 24 days and intravenous for 46 days. In addition, the patient received meropenem and teicoplanin to treat a urinary tract infection and a bacterial aspiration pneumonia. Cerebrospinal fluid trough colistin levels resulted above the MIC of A. baumannii. Colistin cerebrospinal fluid concentration did not increase over the treatment period. Meningitis was cured and A. baumannii eradicated. No side effects from the antimicrobial therapy were observed. In conclusion, this case highlights the issues in treating infections caused by resistant Gram negative bacteria and supports previous findings on the efficacy, pharmacokinetic and tolerability of intravenous and intrathecal colistin treatments. PMID:26543524

  7. Neonatal group A streptococcal meningitis: a case report and review of the literature

    PubMed Central

    Lardhi, Amer A

    2008-01-01

    Introduction Group A streptococcus is a rare cause of neonatal meningitis. A review of MEDLINE database since1966 revealed only 15 documented cases of group A streptococcal meningitis in neonates. Case report A previously healthy 28 days old male neonate presented with a history of irritability, fever, and focal seizures. Cerebrospinal fluid analysis and culture confirmed the diagnosis of group A streptococcal meningitis. The clinical course was complicated by the development of brain abscess. The patient made full recovery following a surgical drainage of the abscess and a 6-week total course of antibiotics. Conclusion Although it is an uncommon organism, clinician should always consider group A streptococcal infection and its potential complications in the differential diagnosis and management of neonatal meningitis. PMID:18710558

  8. Chronic meningitis with intracranial hypertension and bilateral neuroretinitis following Mycoplasma pneumoniae infection.

    PubMed

    Karampatsas, Konstantinos; Patel, Himanshu; Basheer, Sheikh N; Prendergast, Andrew J

    2014-01-01

    A previously well 12-year-old boy presented with a 2-week history of headache, nausea, vomiting and left-sided weakness. He subsequently developed meningism, right abducens nerve palsy, persistent papilloedema and reduced visual acuity in association with a bilateral macular star, consistent with neuroretinitis. Cerebrospinal fluid (CSF) examination indicated chronic meningitis and serological testing confirmed recent Mycoplasma pneumoniae infection, although PCR in CSF was negative. He was treated for aseptic meningitis with ceftriaxone, aciclovir, azithromycin and acetazolamide for intracranial hypertension, with gradual improvement in clinical condition and visual acuity over several weeks. This is the first report of M. pneumoniae chronic meningitis further complicated with bilateral neuroretinitis and intracranial hypertension. Evidence of central nervous system inflammation in the absence of direct infection suggests an immune-mediated pathophysiology. Although the use of macrolides with antibiotic and immunomodulatory activity might be beneficial, it was not possible to ascertain whether it influenced clinical recovery in this case. PMID:25538215

  9. Methods of rapid diagnosis for the etiology of meningitis in adults

    PubMed Central

    Bahr, Nathan C; Boulware, David R

    2014-01-01

    Infectious meningitis may be due to bacterial, mycobacterial, fungal or viral agents. Diagnosis of meningitis must take into account numerous items of patient history and symptomatology along with regional epidemiology and basic cerebrospinal fluid testing (protein, etc.) to allow the clinician to stratify the likelihood of etiology possibilities and rationally select additional diagnostic tests. Culture is the mainstay for diagnosis in many cases, but technology is evolving to provide more rapid, reliable diagnosis. The cryptococcal antigen lateral flow assay (Immuno-Mycologics) has revolutionized diagnosis of cryptococcosis and automated nucleic acid amplification assays hold promise for improving diagnosis of bacterial and mycobacterial meningitis. This review will focus on a holistic approach to diagnosis of meningitis as well as recent technological advances. PMID:25402579

  10. Detection of single bacteria - causative agents of meningitis using raman microscopy

    NASA Astrophysics Data System (ADS)

    Baikova, T. V.; Minaeva, S. A.; Sundukov, A. V.; Svistunova, T. S.; Bagratashvili, V. N.; Alushin, M. V.; Gonchukov, S. A.

    2015-03-01

    Early diagnostics of meningitis is a very topical problem as it is a fulminant disease with a high level of mortality. The progress of this disease is, as a rule, accompanied by the appearance of bacteria in the cerebrospinal fluid (CSF) composition. The examination of the CSF is well known to be the only reliable approach to the identification of meningitis. However, the traditional biochemical analyses are time consuming and not always reliable, simple, and inexpensive, whereas the optical methods are poorly developed. This work is devoted to the study of Raman spectra of several bacterial cultures which are mainly present during meningitis. Raman microscopy is a prompt and noninvasive technique capable of providing reliable information about molecular-level alterations of biological objects at their minimal quantity and size. It was shown that there are characteristic lines in Raman spectra which can be the reliable markers for determination of bacterial form of meningitis at a level of a single bacterium.

  11. Lack of KIs virus DNA in plasma and cerebrospinal fluid in Italy.

    PubMed

    Macera, Lisa; Focosi, Daniele; Manzin, Aldo; Ceccherini Nelli, Luca; Pistello, Mauro; Maggi, Fabrizio

    2015-11-01

    Dear Sirs, Satoh et al. recently screened 516 Japanese blood donors with PCR using primers constructed from the consensus domain of the helicase of positive-stranded RNA viruses. They reported a novel enveloped virus with a circular double-stranded DNA genome (tentatively named KIs virus, KIs-V) (Satoh et al., 2011) occurring in 36 out of the 100 hepatitis E (HEV) antibody-positive donors with elevated alanine aminotransferase (ALT) levels (>60 IU/L). More recently, Biagini et al. failed to find KIs-V in plasma from 576 French blood donors with unknown HEV serostatus and unknown ALT values (Biagini et al., 2012). Based on an HEV seroprevalence of 3-52% in France, the authors suggested an uncommon frequency of KIs-V infection in healthy persons in France. To date, no information has been available on the prevalence of KIs-V DNA in Italy. In the present paper, we analyzed KIs-V in 242 plasma samples of blood donors, transplant recipients, and patients with chronic viral infections, and in 52 cerebrospinal fluid (CSF) samples of patients with different neurological disorders. Informed consent was obtained from all patients and the study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its amendments. Viral DNA extraction was carried out on 200 ?l of plasma or 200 ?l of CSF by using QIAamp DNA blood kit (Qiagen, Hilden, Germany) according to the manufacturer's instructions. Extracted nucleic acids were amplified for KIs-V DNA with the nested PCR protocol developed by Satoh et al. (2011) and used for screening Japanese blood donors. The first and second PCR rounds were designed on 458 and 304 nt-length fragments, respectively. To validate the amplification process, positive controls obtained from plasma dilutions of a synthetic template corresponding to the target sequence were run in each PCR. PCR sensitivity was less than 5 copies of target sequence. Fourteen liver and 16 kidney and/or pancreas transplant recipients were tested before transplantation and at the time after transplantation when viremia levels of TTV were highest, TTV having been validated by our group and others as a marker of functional immune deficiency (Focosi et al., 2014). None of the samples tested positive for KIs-V. At the same time, we also tested 79 healthy blood donors. Since determination of ALT is a mandatory part of on blood donation according to Italian law we could establish that only 2 donors had ALT values >60 IU/L but in any case <80 IU/L: all of them tested negative for KIs-V. No information on HEV status was available and HEV seroprevalence studies are limited in Italy (Arends et al., 2014). However regional studies show prevalences ranging from 2.9% to 8.8% (Masia et al., 2009). We also tested 50 HIV-positive patients, 41 HCV-positive patients, and 42 HBV-positive patients. None of the samples tested positive for KIs-V. Finally, cerebrospinal fluid from 52 patients with different neurological disorders was also tested. All these samples were negative for KIs-V DNA. Thus, although we cannot rule out the possibility that KIs-V circulates in Italy at a very low level and genetically different from the virus found in Japanese population, the results seem to demonstrate a very low prevalence of this novel virus in the Italian population. While the implication of KIs-V in human health remains under debate, extensive regional surveys will help to elucidate the geographical spread of KIs-V and to understand the natural history of the infection in human beings. PMID:26485020

  12. Does the Cerebrospinal Fluid Reflect Altered Redox State But Not Neurotrophic Support Loss in Parkinson's Disease?

    PubMed

    Martín de Pablos, Angel; García-Moreno, José-Manuel; Fernández, Emilio

    2015-10-10

    Alteration in neurotrophic factors support and antioxidant defenses in the central nervous system (CNS) along with deficit of ferritin have been associated with idiopathic Parkinson's disease (PD). The objectives were to analyze in the cerebrospinal fluid (CSF) of patients with PD and controls the following: (i) the levels of the neuroprotectant factors glial cell line-derived neurotrophic factor, persephin, neurturin, and brain-derived neurotrophic factor, (ii) the levels of transforming growth factor-?1 (TGF?1) and transforming growth factor-?2 (TGF?2), proinflammatory factors, (iii) the activity of the antioxidant enzymes glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), catalase, superoxide dismutases (SODs), and peroxiredoxins (PRDxs), and (iv) ferritin levels. The study revealed that, among neurotrophic factors, only TGF?1 levels were found to be enhanced in patients with PD (early, p?

  13. Age-related increase of prostaglandin D(2) synthase concentration and glycation in ovine cerebrospinal fluid.

    PubMed

    Chen, Carl P C; Chen, Ruo Li; Preston, Jane E

    2009-10-01

    Prostaglandin D(2) synthase (PGDS) is a glycoprotein that is exclusively brain derived and is one of the most abundant proteins in the cerebrospinal fluid (CSF). Due to its high CSF specificity, it can be used as a tool for the diagnosis of central nervous system (CNS) disorders. However, several studies have yielded contradictory CSF PGDS concentrations in various CNS neurodegenerative disorders. Sheep CSF samples from different ages were used in this study and 2-dimensional electrophoresis (2-DE) was applied in PGDS identification and concentration calculation. SYPRO Ruby Protein Gel Stain was the staining method used to stain the 2-DE gel protein spots. Pro-Q Emerald 488 Staining for Glycoproteins was used for the staining of glycoproteins. A total of nine PGDS isoforms were identified and CSF total PGDS concentration was calculated to increase linearly by 44% from young (0.9323+/-0.0637mgdL(-1)) to old (1.3669+/-0.0558mgdL(-1)). However, the proportion of CSF total PGDS as a percentage of CSF total protein was discovered to decrease exponentially with age. This was due to the influence of larger age-related increase in CSF albumin concentration (>200% from young to old) as albumin is the most abundant protein in the CSF (>60% of total CSF proteins). Active deglycosylation was not observed in PGDS isoforms during healthy ageing. Some PGDS isoforms were observed to have age-related increase in glycation. These findings suggest that CSF PGDS concentration is increased during healthy ageing and must be taken into consideration when using PGDS as a potential biomarker in diagnosing CNS neurodegenerative disorders. Whether age-related increase in the glycation of some CSF PGDS isoforms will result in detrimental effects on the PGDS protein function needs further investigations. PMID:19595756

  14. Intracranial pressure pulse waveform correlates with aqueductal cerebrospinal fluid stroke volume

    PubMed Central

    Hamilton, Robert; Baldwin, Kevin; Fuller, Jennifer; Vespa, Paul; Hu, Xiao

    2012-01-01

    This study identifies a novel relationship between cerebrospinal fluid (CSF) stroke volume through the cerebral aqueduct and the characteristic peaks of the intracranial pulse (ICP) waveform. ICP waveform analysis has become much more advanced in recent years; however, clinical practice remains restricted to mean ICP, mainly due to the lack of physiological understanding of the ICP waveform. Therefore, the present study set out to shed some light on the physiological meaning of ICP morphological metrics derived by the morphological clustering and analysis of continuous intracranial pulse (MOCAIP) algorithm by investigating their relationships with a well defined physiological variable, i.e., the stroke volume of CSF through the cerebral aqueduct. Seven patients received both overnight ICP monitoring along with a phase-contrast MRI (PC-MRI) of the cerebral aqueduct to quantify aqueductal stroke volume (ASV). Waveform morphological analysis of the ICP signal was performed by the MOCAIP algorithm. Following extraction of morphological metrics from the ICP signal, nine temporal ICP metrics and two amplitude-based metrics were compared with the ASV via Spearman's rank correlation. Of the nine temporal metrics correlated with the ASV, only the width of the P2 region (ICP-Wi2) reached significance. Furthermore, both ICP pulse pressure amplitude and mean ICP did not reach significance. In this study, we showed the width of the second peak (ICP-Wi2) of an ICP pulse wave is positively related to the volume of CSF movement through the cerebral aqueduct. This finding is an initial step in bridging the gap between ICP waveform morphology research and clinical practice. PMID:22995390

  15. Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment

    PubMed Central

    Cassol, Edana; Misra, Vikas; Dutta, Anupriya; Morgello, Susan; Gabuzda, Dana

    2014-01-01

    Objective(s): HIV-associated neurocognitive disorders (HAND) remain prevalent in HIV-infected patients on antiretroviral therapy (ART), but the underlying mechanisms are unclear. Some features of HAND resemble those of age-associated cognitive decline in the absence of HIV, suggesting that overlapping mechanisms may contribute to neurocognitive impairment. Design: Cross-sectional analysis of cerebrospinal fluid (CSF) from 100 individuals (46 HIV-positive patients and 54 HIV-negative controls). Methods: Untargeted CSF metabolite profiling was performed using liquid/gas chromatography followed by mass spectrometry. Cytokine profiling was performed by Bioplex. Bioinformatic analyses were performed in Metaboanalyst and R. Results: Alterations in the CSF metabolome of HIV patients on ART mapped to pathways associated with neurotransmitter production, mitochondrial function, oxidative stress, and metabolic waste. Many CSF metabolites altered in HIV overlapped with those altered with advanced age in HIV-negative controls, suggesting a pattern indicative of accelerated aging. Machine learning models identified neurotransmitters (glutamate, N-acetylaspartate), markers of glial activation (myo-inositol), and ketone bodies (beta-hydroxybutyric acid, 1,2-propanediol) as top-ranked classifiers of HAND. These CSF metabolites correlated with worse neurocognitive test scores, plasma inflammatory biomarkers [interferon (IFN)-?, IFN-?, interleukin (IL)-8, IL-1?, IL-6, IL-2Ra], and intrathecal IFN responses (IFN-? and kynurenine : tryptophan ratio), suggesting inter-relationships between systemic and intrathecal inflammation and metabolic alterations in CSF. Conclusions: Alterations in the CSF metabolome of HIV patients on ART suggest that persistent inflammation, glial responses, glutamate neurotoxicity, and altered brain waste disposal systems contribute to mechanisms involved in HAND that may be augmented with aging. PMID:24752083

  16. Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta).

    PubMed

    Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P; Steffen-Smith, Emilie A; Saleem, Kadharbatcha; Thomas, Marvin L; Cruz, Rafael; Warren, Katherine E

    2015-02-01

    Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates. PMID:25730761

  17. Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer.

    PubMed

    Lee, Jin Sun; Melisko, Michelle E; Magbanua, Mark Jesus M; Kablanian, Andrea T; Scott, Janet H; Rugo, Hope S; Park, John W

    2015-11-01

    Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson's r = 0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls (p = 0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment. PMID:26520840

  18. Cerebrospinal fluid protein dynamic driver network: At the crossroads of brain tumorigenesis.

    PubMed

    Tan, Zhou; Liu, Rui; Zheng, Le; Hao, Shiying; Fu, Changlin; Li, Zhen; Deng, Xiaohong; Jang, Taichang; Merchant, Milton; Whitin, John C; Guo, Minyi; Cohen, Harvey J; Recht, Lawrence; Ling, Xuefeng B

    2015-07-15

    To get a better understanding of the ongoing in situ environmental changes preceding the brain tumorigenesis, we assessed cerebrospinal fluid (CSF) proteome profile changes in a glioma rat model in which brain tumor invariably developed after a single in utero exposure to the neurocarcinogen ethylnitrosourea (ENU). Computationally, the CSF proteome profile dynamics during the tumorigenesis can be modeled as non-smooth or even abrupt state changes. Such brain tumor environment transition analysis, correlating the CSF composition changes with the development of early cellular hyperplasia, can reveal the pathogenesis process at network level during a time before the image detection of the tumors. In our controlled rat model study, matched ENU- and saline-exposed rats' CSF proteomics changes were quantified at approximately 30, 60, 90, 120, 150 days of age (P30, P60, P90, P120, P150). We applied our transition-based network entropy (TNE) method to compute the CSF proteome changes in the ENU rat model and test the hypothesis of the critical transition state prior to impending hyperplasia. Our analysis identified a dynamic driver network (DDN) of CSF proteins related with the emerging tumorigenesis progressing from the non-hyperplasia state. The DDN associated leading network CSF proteins can allow the early detection of such dynamics before the catastrophic shift to the clear clinical landmarks in gliomas. Future characterization of the critical transition state (P60) during the brain tumor progression may reveal the underlying pathophysiology to device novel therapeutics preventing tumor formation. More detailed method and information are accessible through our website at http://translationalmedicine.stanford.edu. PMID:25982164

  19. Repair and prevention of cerebrospinal fluid leakage in transsphenoidal surgery: a sphenoid sinus mucosa technique.

    PubMed

    Amano, Kosaku; Hori, Tomokatsu; Kawamata, Takakazu; Okada, Yoshikazu

    2016-01-01

    Cerebrospinal fluid (CSF) leakage is a common but sometimes serious complication after transsphenoidal surgery (TSS). To avoid this postsurgical complication, we usually repair the CSF leaking area using an autologous material, such as fat, fascia, or muscle graft and sometimes nasonasal septal flap. In this report, we propose a technique using a novel autologous material, sphenoid sinus mucosa (SSM), to repair intraoperative CSF leakage or prevent it postoperatively. On 26 February 2007, we introduced the technique of using SSM to repair or prevent CSF leakage in TSS. Until 30th of June 2014, we performed 500 TSSs for patients with pituitary or parasellar lesions. They were 195 men and 305 women with a mean age of 48.5 years (range, 5-85 years). We used SSM for patching or suturing the arachnoid laceration or dural defect, in lieu of fat or fascia harvested from abdomen or thigh, or made pedicle flap of SSM instead of nasonasal septal flap to cover the sellar floor. Comparing the previous 539 cases not using these techniques before 26 February 2007, intraoperative CSF leakage increased from 49 to 69.4 % (p?

  20. Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

    PubMed Central

    Cusato, Maria; Accetta, Giovanni; Marinò, Valeria; Procaccio, Francesco; Del Gaudio, Alfredo; Iotti, Giorgio A.; Regazzi, Mario

    2012-01-01

    Intraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2?) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ?5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 ?g/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 ?g/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ?5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent. PMID:22687507

  1. Development of a Cerebrospinal Fluid Lateral Reservoir Model in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P; Steffen-Smith, Emilie A; Saleem, Kadharbatcha; Thomas, Marvin L; Cruz, Rafael; Warren, Katherine E

    2015-01-01

    Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates. PMID:25730761

  2. Cystatin C as a cerebrospinal fluid biomarker for pain in humans.

    PubMed

    Mannes, Andrew J; Martin, Brian M; Yang, Hsiu-Ying T; Keller, Jason M; Lewin, Stacy; Gaiser, Robert R; Iadarola, Michael J

    2003-04-01

    Through a process of subtraction cloning and differential hybridization, we previously identified several new genes whose expression was induced by peripheral inflammation. One of these coded for cystatin C, a secreted cysteine protease inhibitor in the cystatin superfamily. We hypothesized that, concurrent with increased expression in dorsal horn, increased secretion would elevate the cystatin C content in cerebrospinal fluid (CSF) during active pain states. Alterations were assessed by immunoassay and by surface enhanced laser desorption ionization (SELDI) mass spectrometry with either reverse phase or immobilized anti-cystatin C antibody surfaces using CSF from ten age-matched obstetrical patients at term. Five control subjects were scheduled for an elective caesarian section and were not in pain. Another five subjects were in labor for 8.9+/-1h and were in severe pain as assessed with a visual analog scale and the McGill short form questionnaire. The level of cystatin C as measured by immunoassay in the non-pain patients was 2.77+/-0.75 microg/ml and in the pain patients 5.36+/-0.92 microg/ml (P<0.02). The elevation occurred without significant change in total CSF protein or beta-endorphin content. The cystatin C increase also was detectable by SELDI with either raw CSF or after antibody capture. These data are consistent with our previous animal study and the idea that persistent pain induces the synthesis and release of cystatin C in dorsal spinal cord, the surplus of which overflows into the CSF. PMID:12670666

  3. Cerebrospinal Fluid JC Virus Antibody Index for Diagnosis of Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

    PubMed Central

    Warnke, Clemens; von Geldern, Gloria; Markwerth, Philipp; Dehmel, Thomas; Hoepner, Robert; Gold, Ralf; Pawlita, Michael; Kümpfel, Tania; Mäurer, Mathias; Stangel, Martin; Wegner, Florian; Hohlfeld, Reinhard; Straeten, Vera; Limmroth, Volker; Weber, Thomas; Hermsen, Derik; Kleinschnitz, Christoph; Hartung, Hans-Peter; Wattjes, Mike P.; Anders, Svenningson; Major, Eugene; Olsson, Tomas; Kieseier, Bernd C.; Adams, Ortwin

    2014-01-01

    Objective Progressive multifocal leukoencephalopathy (PML), caused by JC virus (JCV), can occur in patients receiving natalizumab for multiple sclerosis (MS). JCV detection by quantitative polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF), or brain biopsy, is required for probable or definite diagnosis of PML. However, in some patients only low levels of JCV DNA (<100 copies/ml) are present in CSF, making the diagnosis challenging. Our objective was to assess the complementary value of a CSF JCV antibody index (AIJCV) in the diagnosis of natalizumab-associated PML. Methods AIJCV was assessed in 37 cases of natalizumab-associated PML and 89 MS-patients treated with natalizumab without PML. Sera and CSF were tested in a capture enzyme-linked immunosorbent assay, using JCV-VP1 fused to glutathione S-transferase as antigen. Albumin levels and total immunoglobulin G concentration were determined by immunonephelometry, and the AIJCV was calculated as published. Results Twenty-six of 37 (70%) patients with natalizumab-associated PML exhibited an AIJCV > 1.5, whereas this was seen in none of the controls (p < 0.0001). At time of the first positive qPCR for JCV DNA, 11 of 20 (55%) patients with natalizumab-associated PML had an AIJCV > 1.5. JCV DNA levels of <100 copies/ml were seen in 14 (70%) of these 20 patients, of whom 8 (57%) demonstrated an AIJCV > 1.5. Interpretation Determination of the AIJCV could be an added tool in the diagnostic workup for PML and should be included in the case definition of natalizumab-associated PML. PMID:24729444

  4. TDP-43 in Cerebrospinal Fluid of Patients With Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

    PubMed Central

    Steinacker, Petra; Hendrich, Corinna; Sperfeld, Anne D.; Jesse, Sarah; von Arnim, Christine A. F.; Lehnert, Stefan; Pabst, Alice; Uttner, Ingo; Tumani, Hayrettin; Lee, Virginia M.-Y.; Trojanowski, John Q.; Kretzschmar, Hans A.; Ludolph, Albert; Neumann, Manuela; Otto, Markus

    2009-01-01

    Background Recently, TAR DNA-binding protein 43 (TDP-43) was identified as the major component of ubiquitin-positive tau-negative neuronal and glial inclusions in the most common form of frontotemporal lobar degeneration (FTLD) and in amyotrophic lateral sclerosis (ALS). It was demonstrated that different TDP-43 profiles correspond to clinical phenotypes of FTLD or ALS subgroups, and the differential diagnostic potential of TDP-43 was suggested. Objectives To examine TDP-43 in cerebrospinal fluid (CSF) and to analyze whether it could serve as a diagnostic marker. Design We characterized CSF TDP-43 by immunoblot using different TDP-43 antibodies and determined the relative TDP-43 levels in CSF samples from patients. Setting Academic research. Patients Twelve patients with FTLD, 15 patients with ALS, 9 patients with ALS plus FTLD, 3 patients with ALS plus additional signs of frontal disinhibition, and 13 control subjects. Main Outcome Measures Results of TDP-43 immunoblot. Results Polyclonal TDP-43 antibodies recognized a 45-kDa band in all analyzed samples. Two monoclonal and N-terminus—specific antibodies did not detect any specific bands, but C-terminus—specific antibodies detected a 45-kDa band and additional bands at approximately 20 kDa in all CSF samples. Relative quantification of 45-kDa bands revealed significant differences among the diagnostic groups (P=.046). Specifically, patients with ALS (P=.03) and FTLD (P=.02) had higher TDP-43 levels than controls but with a prominent overlap of values. Conclusion Although there is no evidence of pathologically altered TDP-43 proteins in CSF, TDP-43 levels in CSF might aid in characterizing subgroups of patients across the ALS and FTLD disease spectrum. PMID:19001167

  5. Specific absorbed fractions of energy from internal photon sources in brain tumor and cerebrospinal fluid

    SciTech Connect

    Evans, J.F. )); Stubbs, J.B. )

    1995-03-01

    Transferrin, radiolabeled with In-111, can be coinjected into glioblastoma multiforme lesions, and subsequent scintigraphic imaging can demonstrate the biokinetics of the cytotoxic transferrin. The administration of [sup 111]In transferrin into a brain tumor results in distribution of radioactivity in the brain, brain tumor, and the cerebrospinal fluid (CSF). Information about absorbed radiation doses to these regions, as well as other nearby tissues and organs, is important for evaluating radiation-related risks from this procedure. The radiation dose is usually estimated for a mathematical representation of the human body. We have included source/target regions for the eye, lens of the eye, spinal column, spinal CSF, cranial CSF, and a 100-g tumor within the brain of an adult male phantom developed by Cristy and Eckerman. The spinal column, spinal CSF, and the eyes have not been routinely included in photon transport simulations. Specific absorbed fractions (SAFs) as a function of photon energy were calculated using the ALGAMP computer code, which utilizes Monte Carlo techniques for simulating photon transport. The ALGAMP code was run three times, with the source activity distributed uniformly within the tumor, cranial CSF, and the spinal CSF volumes. These SAFs, which were generated for 12 discrete photon energies ranging from 0.01 to 4.0 MeV, were used with decay scheme data to calculate [ital S]-values needed for estimating absorbed doses. [ital S]-values for [sup 111]In are given for three source regions (brain tumor, cranial CSF, and spinal CSF) and all standard target regions/organs, the eye and lens, as well as to tissues within these source regions. [ital S]-values for the skeletal regions containing active marrow are estimated. These results are useful in evaluating the radiation doses from intracranial administration of [sup 111]In transferrin.

  6. BACE1 activity in cerebrospinal fluid and its relation to markers of AD pathology.

    PubMed

    Mulder, Sandra D; van der Flier, Wiesje M; Verheijen, Jan H; Mulder, Cees; Scheltens, Philip; Blankenstein, Marinus A; Hack, C Erik; Veerhuis, Robert

    2010-01-01

    Several studies have shown that reduced amyloid-beta 1-42 (Abeta(42)) and increased tau levels in cerebrospinal fluid (CSF) reflect increased Alzheimer's disease (AD) pathology in the brain. beta-site APP cleaving enzyme (BACE1) is thought to be the major beta-secretase involved in Abeta production in the brain, and therefore we investigated the relation between BACE1 activity and CSF markers Abeta(40), Abeta(42), total tau (t-tau), and tau phosphorylated at threonine 181 (p-tau) in CSF of control (n=12), mild cognitive impairment (n=18), and AD (n=17) subjects. Patients were classified according to their Abeta(42), t-tau, and p-tau CSF biomarker levels, with either an AD-like biomarker profile (two or three biomarkers abnormal: Abeta(42) < 495 pg/ml in combination with t-tau > 356 pg/ml, and/or p-tau > 54 pg/ml) or a normal biomarker profile (

  7. Biochemical, histological and functional correction of mucopolysaccharidosis type IIIB by intra-cerebrospinal fluid gene therapy.

    PubMed

    Ribera, Albert; Haurigot, Virginia; Garcia, Miguel; Marcó, Sara; Motas, Sandra; Villacampa, Pilar; Maggioni, Luca; León, Xavier; Molas, Maria; Sánchez, Víctor; Muñoz, Sergio; Leborgne, Christian; Moll, Xavier; Pumarola, Martí; Mingozzi, Federico; Ruberte, Jesús; Añor, Sònia; Bosch, Fatima

    2015-04-01

    Gene therapy is an attractive tool for the treatment of monogenic disorders, in particular for lysosomal storage diseases (LSD) caused by deficiencies in secretable lysosomal enzymes in which neither full restoration of normal enzymatic activity nor transduction of all affected cells are necessary. However, some LSD such as Mucopolysaccharidosis Type IIIB (MPSIIIB) are challenging because the disease's main target organ is the brain and enzymes do not efficiently cross the blood-brain barrier even if present at very high concentration in circulation. To overcome these limitations, we delivered AAV9 vectors encoding for ?-N-acetylglucosaminidase (NAGLU) to the Cerebrospinal Fluid (CSF) of MPSIIIB mice with the disease already detectable at biochemical, histological and functional level. Restoration of enzymatic activity in Central Nervous System (CNS) resulted in normalization of glycosaminoglycan content and lysosomal physiology, resolved neuroinflammation and restored the pattern of gene expression in brain similar to that of healthy animals. Additionally, transduction of the liver due to passage of vectors to the circulation led to whole-body disease correction. Treated animals also showed reversal of behavioural deficits and extended lifespan. Importantly, when the levels of enzymatic activity were monitored in the CSF of dogs following administration of canine NAGLU-coding vectors to animals that were either naïve or had pre-existing immunity against AAV9, similar levels of activity were achieved, suggesting that CNS efficacy would not be compromised in patients seropositive for AAV9. Our studies provide a strong rationale for the clinical development of this novel therapeutic approach as the treatment for MPSIIIB. PMID:25524704

  8. Cerebrospinal fluid A?40 is similarly reduced in patients with Frontotemporal Lobar Degeneration and Alzheimer's Disease.

    PubMed

    Baldeiras, Inês; Santana, Isabel; Leitão, Maria João; Ribeiro, Maria Helena; Pascoal, Rui; Duro, Diana; Lemos, Raquel; Santiago, Beatriz; Almeida, Maria Rosário; Oliveira, Catarina Resende

    2015-11-15

    Cerebrospinal fluid (CSF) biomarkers have been increasingly studied for dementia diagnosis, however the accuracy to distinguish between different forms of dementia is still unsatisfactory. In this study, the added value of another CSF A?-peptide (A?40), along with the core CSF markers t-Tau, p-Tau, and A?42, in the discrimination between two large dementia groups of Frontotemporal Lobar Degeneration (FTLD; n=107), Alzheimer's Disease (AD; n=107) and non-demented subjects (n=33) was evaluated. In FTLD, t-Tau and p-Tau were significantly increased in relation to controls, but lower than in AD, while A?42 was similar in FTLD and controls, but higher than in AD. Equally reduced A?40 levels were seen in both dementia groups, and therefore the combination of A?40 with core CSF biomarkers optimally discriminated FTLD and AD patients from controls. A?42 and t-Tau were selected as the best biomarker subset to differentiate FTLD from AD, with no added value of A?40 to the model. Diagnostic accuracy between FTLD and AD was still sub-optimal, with a significant percentage (23%) of FTLD patients, in particularly women, carrying an ApoE-?4 allele, showing a CSF-AD biomarkers profile. Although CSF A?40 does not appear to have an additional value in the distinction between FTLD and AD, it increases the discrimination between subjects with dementia from controls. A CSF-AD biomarker profile can be seen in patients with a clinical phenotype of FTLD, reinforcing the need for autopsy confirmation. PMID:26388316

  9. Acute Phase Proteins in Cerebrospinal Fluid from Dogs with Naturally-Occurring Spinal Cord Injury.

    PubMed

    Anderson, Kimberly M; Welsh, C Jane; Young, Colin; Levine, Gwendolyn J; Kerwin, Sharon C; Boudreau, C Elizabeth; Reyes, Ismael; Mondragon, Armando; Griffin, John F; Cohen, Noah D; Levine, Jonathan M

    2015-11-01

    Spinal cord injury (SCI) affects thousands of people each year and there are no treatments that dramatically improve clinical outcome. Canine intervertebral disc herniation is a naturally-occurring SCI that has similarities to human injury and can be used as a translational model for evaluating therapeutic interventions. Here, we characterized cerebrospinal fluid (CSF) acute phase proteins (APPs) that have altered expression across a spectrum of neurological disorders, using this canine model system. The concentrations of C-reactive protein (CRP), haptoglobin (Hp), alpha-1-glycoprotein, and serum amyloid A were determined in the CSF of 42 acutely injured dogs, compared with 21 healthy control dogs. Concentrations of APPs also were examined with respect to initial injury severity and motor outcome 42 d post-injury. Hp concentration was significantly higher (p<0.0001) in the CSF of affected dogs, compared with healthy control dogs. Additionally, the concentrations of CRP and Hp were significantly (p=0.0001 and p=0.0079, respectively) and positively associated with CSF total protein concentration. The concentrations of CRP and Hp were significantly higher (p=0.0071 and p=0.0197, respectively) in dogs with severe injury, compared with those with mild-to-moderate SCI, but there was no significant correlation between assessed CSF APP concentrations and 42 d motor outcome. This study demonstrated that CSF APPs were dysregulated in dogs with naturally-occurring SCI and could be used as markers for SCI severity. As Hp was increased following severe SCI and is neuroprotective across a number of model systems, it may represent a viable therapeutic target. PMID:26186466

  10. Bilateral meningoencephaloceles with cerebrospinal fluid rhinorrhea after facial advancement in the Crouzon syndrome

    PubMed Central

    Panuganti, Bharat A.; Leach, Matthew

    2015-01-01

    Background: Cerebrospinal fluid (CSF) rhinorrhea and encephaloceles are rare complications of craniofacial advancement procedures performed in patients with craniofacial dysostoses (CD) to address the ramifications of their midface hypoplasia including obstructed nasal airway, exorbitism, and impaired mastication. Surgical repair of this CSF rhinorrhea is complicated by occult elevations in intracranial pressure (ICP), potentially necessitating open, transcranial repair. We report the first case in otolaryngology literature of a patient with Crouzon syndrome with late CSF rhinorrhea and encephalocele formation after previous LeFort III facial advancement surgery. Objectives: Describe the case of a patient with Crouzon syndrome who presented with CSF rhinorrhea and encephaloceles as complications of Le Fort III facial advancement surgery. Review the literature pertaining to the incidence and management of post-operative CSF rhinorrhea and encephaloceles. Analyze issues related to repair of these complications, including occult elevations in ICP, the utility of perioperative CSF shunts, and the importance of considering alternative repair schemes to the traditional endonasal, endoscopic approach. Methods: Review of the literature describing CSF rhinorrhea and encephalocele formation following facial advancement in CD, focusing on management strategies. Results: CSF rhinorrhea and encephalocele formation are rare complications of craniofacial advancement procedures. Occult elevations in ICP complicate the prospect of permanent surgical repair, potentially necessitating transcranial repair and the use of CSF shunts. Though no consensus exists regarding the utility of perioperative CSF drains, strong associations exist between elevated ICP and failed surgical repair. Additionally, the anatomic changes in the frontal and ethmoid sinuses after facial advancement present a challenge to endoscopic repair. Conclusion: Otolaryngologists should be aware of the possibility of occult elevations in ICP and sinonasal anatomic abnormalities when repairing CSF rhinorrhea in patients with CD. Clinicians should consider CSF shunt placement and carefully weigh the advantages of the transcranial approach versus endonasal, endoscopic techniques. PMID:26302737

  11. Cerebrospinal fluid synaptic proteins as useful biomarkers in tyrosine hydroxylase deficiency.

    PubMed

    Ortez, C; Duarte, S T; Ormazábal, A; Serrano, M; Pérez, A; Pons, R; Pineda, M; Yapici, Z; Fernández-Álvarez, E; Domingo-Jiménez, R; De Castro, P; Artuch, R; García-Cazorla, A

    2015-01-01

    Tyrosine hydroxylase (TH) deficiency is an inborn error of dopamine biosynthesis and a cause of early parkinsonism. Two clinical phenotypes have been described. Type "B": early onset severe encephalopathy; type "A": later onset, less severe and better response to L-dopa. We aimed to study the expression of several key dopaminergic and gabaergic synaptic proteins in the cerebrospinal fluid (CSF) of a series of patients with TH deficiency and their possible relation with the clinical phenotype and response to L-DOPA. Dopamine transporter (DAT), D2-receptor and vesicular monoamine transporter (VMAT2) were measured in the CSF of 10 subjects with TH deficiency by Western blot analysis. In 3 patients, data of pre- and post-treatment with L-DOPA were available, and in one of them, GABA vesicular transporter was determined. Results were compared to an age-matched control population. The concentration of D2-receptors in CSF was significantly higher in patients with TH deficiency than in controls. Similarly, DAT and vesicular monoamine transporter type 2 were up-regulated. Studies performed before L-DOPA, and on L-DOPA therapy showed a paradoxical response with D2 receptor expression increase as L-Dopa doses and homovanillic concentration gradually raised in a B phenotype patient. The opposite results were found in two patients with A phenotype. However, this is a very small sample, and further studies are needed to conclude robust differences between phenotypes. Synaptic proteins are detectable in the CSF and their quantification can be useful for understanding the pathophysiology of neurotransmitter defects and potentially to adjust and personalize treatments in the future. PMID:25468651

  12. Fructose Levels Are Markedly Elevated in Cerebrospinal Fluid Compared to Plasma in Pregnant Women

    PubMed Central

    Hwang, Janice J.; Johnson, Andrea; Cline, Gary; Belfort-DeAguiar, Renata; Snegovskikh, Denis; Khokhar, Babar; Han, Christina S.; Sherwin, Robert S.

    2015-01-01

    Background Fructose, unlike glucose, promotes feeding behavior in rodents and its ingestion exerts differential effects in the human brain. However, plasma fructose is typically 1/1000th of glucose levels and it is unclear to what extent fructose crosses the blood-brain barrier. We investigated whether local endogenous central nervous system (CNS) fructose production from glucose via the polyol pathway (glucose?sorbitol?fructose) contributes to brain exposure to fructose. Methods In this observational study, fasting glucose, sorbitol and fructose concentrations were measured using gas-chromatography-liquid mass spectroscopy in cerebrospinal fluid (CSF), maternal plasma, and venous cord blood collected from 25 pregnant women (6 lean, 10 overweight/obese, and 9 T2DM/gestational DM) undergoing spinal anesthesia and elective cesarean section. Results As expected, CSF glucose was ~60% of plasma glucose levels. In contrast, fructose was nearly 20-fold higher in CSF than in plasma (p < 0.001), and CSF sorbitol was ~9-times higher than plasma levels (p < 0.001). Moreover, CSF fructose correlated positively with CSF glucose (? 0.45, p = 0.02) and sorbitol levels (? 0.75, p < 0.001). Cord blood sorbitol was also ~7-fold higher than maternal plasma sorbitol levels (p = 0.001). There were no differences in plasma, CSF, and cord blood glucose, fructose, or sorbitol levels between groups. Conclusions These data raise the possibility that fructose may be produced endogenously in the human brain and that the effects of fructose in the human brain and placenta may extend beyond its dietary consumption. PMID:26035307

  13. Incidence and management of cerebrospinal fluid fistulas in 336 multilevel laminectomies with noninstrumented fusions

    PubMed Central

    Epstein, Nancy E.

    2015-01-01

    Background: The incidence (e.g., 3–27%) and the types of cerebrospinal fluid (CSF) fistulas occurring during multilevel lumbar laminectomy with noninstrumented spinal fusions varies. Methods: From 2000 to 2015, we retrospectively evaluated the incidence/etiologies of CSF fistulas occurring for 336 patients undergoing average 4.7 laminectomies with average 1.4 level noninstrumented fusions over a 15 year period. The varied etiologies of CSF leaks included; ossification of the yellow ligament (OYL) extending through the dura, postoperative surgical scar, iatrogenic traumatic leak, epidural steroid injections (ESI), resection of synovial cysts, and the removal of intradural tumors. Techniques for primary repairs included combinations of; 7-0 Gore-Tex (Newark, Delaware, USA) sutures, micro-dural staples, muscle patch/other (e.g., bovine pericardial) grafts, fibrin sealants/glues (e.g., Tisseel; Baxter International Inc., Westlake Village, CA, USA), and Duragen (Integra LifeSciences, Hawthorne, NY, USA) including both the thin and suturable types. Results: The etiologies of CSF fistulas in descending order included: Epidural spinal injections (ESI) (7 patients), synovial cysts (6 patients), OYL (5 patients), and equally for postoperative scar and intradural tumors (3 patients). CSF fistulas occurred in 24 (7.14%) of 336 patients; this frequency was reduced to 4.2% when ESI and intradural tumors were excluded. Conclusion: CSF fistulas occurred in 7.14% of 336 patients undergoing average 4.7 multilevel laminectomies with average 1.4 level noninstrumented fusions attributed to a lumbar stenosis with mild/moderate instability. The dural repair addressed seven prior ESI, six synovial cysts, five OYL, and operative scarring and intradural tumors (three apiece). Knowing the pathologies contributing to CSF fistulas should help the surgeon to better anticipate and treat these fistulas. PMID:26605107

  14. 1H-NMR-Based Metabolomic Analysis of Cerebrospinal Fluid From Adult Bilateral Moyamoya Disease

    PubMed Central

    Jeon, Jin Pyeong; Yun, Taeho; Jin, Xing; Cho, Won-Sang; Son, Young-Je; Bang, Jae Seung; Kang, Hyun-Seung; Oh, Chang Wan; Kim, Jeong Eun; Park, Sunghyouk

    2015-01-01

    Abstract Although metabolomics has been increasingly used to observe metabolic pattern and disease-specific metabolic markers, metabolite profiling for moyamoya disease (MMD) has not yet been done in adults. This study investigated cerebrospinal fluid (CSF) metabolites specific to bilateral MMD (B-MMD) and compared them to those of unilateral MMD (U-MMD) or atherosclerotic stenosis with hydrogen-1 nuclear magnetic resonance spectroscopy to identify metabolic biomarkers associated with MMD in adults. CSF samples of B-MMD (n?=?29), U-MMD (n?=?11), and atherosclerotic cerebrovascular disease (ACVD) (n?=?8) were recruited. Principal component analysis, partial least square discriminant analysis, and orthogonal projections to latent structure discriminant analysis (OPLS-DA) were done for the comparisons. Diagnostic performance was acquired by prediction of 1 left-out sample from the distinction model constructed with the rest of the samples. B-MMD showed an increase in glutamine (P?

  15. Modified Graded Repair of Cerebrospinal Fluid Leaks in Endoscopic Endonasal Transsphenoidal Surgery

    PubMed Central

    Park, Jae-Hyun; Choi, Jai Ho; Kim, Young-Il; Kim, Sung Won

    2015-01-01

    Objective Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time-consuming. Methods Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage. Results Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned. Conclusion Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en-bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks. PMID:26279811

  16. Insulin resistance is associated with higher cerebrospinal fluid tau levels in asymptomatic APOE ?4 carriers

    PubMed Central

    Starks, Erika J.; O'Grady, J. Patrick; Hoscheidt, Siobhan M.; Racine, Annie M.; Carlsson, Cindy M.; Zetterberg, Henrik; Blennow, Kaj; Okonkwo, Ozioma C.; Puglielli, Luigi; Asthana, Sanjay; Dowling, N. Maritza; Gleason, Carey E.; Anderson, Rozalyn M.; Davenport-Sis, Nancy J.; DeRungs, LeAnn M.; Sager, Mark A.; Johnson, Sterling C.; Bendlin, Barbara B.

    2015-01-01

    Background Insulin resistance (IR) is linked with the occurrence of pathological features observed in Alzheimer's disease (AD), including neurofibrillary tangles and amyloid plaques. However, the extent to which IR is associated with AD pathology in the cognitively asymptomatic stages of preclinical AD remains unclear. Objective To determine the extent to which IR is linked with amyloid and tau pathology in late-middle-age. Method Cerebrospinal fluid (CSF) samples collected from 113 participants enrolled in the Wisconsin Registry for Alzheimer's Prevention study (mean age = 60.6 years), were assayed for AD-related markers of interest: A?42, P-Tau181, and T-Tau. IR was determined using the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). Linear regression was used to test the effect of IR, and APOE ?4, on tau and amyloid pathology. We hypothesized that greater IR would be associated with higher CSF P-Tau181 and T-Tau, and lower CSF A?42. Results No significant main effects of HOMA-IR on P-Tau181, T-Tau, or A?42 were observed; however, significant interactions were observed between HOMA-IR and APOE ?4 on CSF markers related to tau. Among APOE ?4 carriers, higher HOMA-IR was associated with higher P-Tau181 and T-Tau. Among APOE ?4 non-carriers, HOMA-IR was negatively associated with P-Tau181 and T-Tau. We found no effects of IR on A?42 levels in CSF. Conclusion IR among asymptomatic APOE ?4 carriers was associated with higher P-Tau181 and T-Tau in late-middle age. The results suggest that IR may contribute to tau-related neurodegeneration in preclinical AD. The findings may have implications for developing prevention strategies aimed at modifying IR in mid-life. PMID:25812851

  17. Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

    PubMed Central

    Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

    2008-01-01

    This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion PMID:18479516

  18. [Iatrogenic meningitis after diagnosis lumbar puncture: 3 cases reports in the paediatric Children's Hospital of Tunis].

    PubMed

    Smaoui, H; Hariga, D; Hajji, N; Bouziri, A; Ben Jaballah, N; Barsaoui, S; Bousnina, S; Sammoud, A; Kechrid, A

    2011-02-01

    We have collected cases of iatrogenic meningitis managed in the Children's Hospital of Tunis, between January 1998 and December 2006. Clinical information about each patient were collected, all bacterial samples were investigated in the microbiology laboratory of the hospital. Bacterial isolates were identified according to conventional criteria. In the interval under study, we recorded three cases of iatrogenic meningitis after lumbar puncture. Two cases occurred in newborn admitted for suspicion of neonatal infection and one in a 2-month-old infant admitted for exploration of hyperpyretic convulsion. In all patients, the initial cerebrospinal fluid was normal. All patients developed symptoms of acute meningitis within 72 hours after lumbar puncture; the second cerebrospinal fluid was, then, typical for purulent meningitis. The causal agents isolated in the three cases were Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens, all resistant to beta-lactams by extended spectrum beta-lactamase production. The use of quinolones was required in all cases. Different complications were recorded: hydrocephalus and brain abscess in one case, respiratory and hemodynamic failure managed in the intensive care unit in the second, and brain hygroma in the third case. This study shows high morbidity of iatrogenic meningitis. Simple aseptic precautions undertaken before the procedure of lumbar puncture can prevent such cases. The urgent need for increasing the awareness among medical personnel in hospitals of developing countries cannot be overemphasized. PMID:21103965

  19. Herpes zoster with skin lesions and meningitis caused by 2 different genotypes of the Oka varicella-zoster virus vaccine.

    PubMed

    Levin, Myron J; DeBiasi, Roberta L; Bostik, Vanda; Schmid, D Scott

    2008-11-15

    A previously healthy boy who had received varicella vaccine developed herpes zoster with meningitis. The vaccine strain recovered from scabs of 3 skin lesions had the wild-type allele at position 108111, a vaccine marker never previously associated with vaccine-associated adverse events. The vaccine strain from cerebrospinal fluid also contained mutations never previously observed at vaccine-associated single nucleotide polymorphisms that would alter amino acid sequences in ORF54 and ORF59. The presence of distinct strains in skin lesions and cerebrospinal fluid indicate that >1 variant strain may reactivate to cause herpes zoster. PMID:18826373

  20. Scrub Typhus Meningitis in South India — A Retrospective Study

    PubMed Central

    Viswanathan, Stalin; Muthu, Vivekanandan; Iqbal, Nayyar; Remalayam, Bhavith; George, Tarun

    2013-01-01

    Background Scrub typhus is prevalent in India although definite statistics are not available. There has been only one study on scrub typhus meningitis 20 years ago. Most reports of meningitis/meningoencephalitis in scrub typhus are case reports Methods A retrospective study done in Pondicherry to extract cases of scrub typhus admitted to hospital between February 2011 and January 2012. Diagnosis was by a combination of any one of the following in a patient with an acute febrile illness- a positive scrub IgM ELISA, Weil-Felix test, and an eschar. Lumbar puncture was performed in patients with headache, nuchal rigidity, altered sensorium or cranial nerve deficits. Results Sixty five cases of scrub typhus were found, and 17 (17/65) had meningitis. There were 33 males and 32 females. Thirteen had an eschar. Median cerebrospinal fluid (CSF) cell count, lymphocyte percentage, CSF protein, CSF glucose/blood glucose, CSF ADA were 54 cells/µL, 98%, 88 mg/dL, 0.622 and 3.5 U/mL respectively. Computed tomography was normal in patients with altered sensorium and cranial nerve deficits. Patients with meningitis had lesser respiratory symptoms and signs and higher urea levels. All patients had received doxycycline except one who additionally received chloramphenicol. Conclusion Meningitis in scrub typhus is mild with quick and complete recovery. Clinical features and CSF findings can mimic tuberculous meningitis, except for ADA levels. In the Indian context where both scrub typhus and tuberculosis are endemic, ADA and scrub IgM may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis. PMID:23799119

  1. Leukemic meningitis in a patient with hairy cell leukemia. A case report

    SciTech Connect

    Wolfe, D.W.; Scopelliti, J.A.; Boselli, B.D.

    1984-09-15

    Central nervous system involvement has not previously been described in patients with hairy cell leukemia (HCL). A patient is reported who presented with meningeal involvement as his initial symptom of HCL. Diagnosis was established by morphologic and cytochemical studies of his cerebrospinal fluid (CSF) and bone marrow. Treatment with whole-brain irradiation and intrathecal chemotherapy was successful in clearing leukemic cells from the CSF with resolution of symptoms.

  2. Mass spectrometric analysis of cerebrospinal fluid protein for glioma and its clinical application

    PubMed Central

    Yu, Jiekai; Shen, Hong; Zhang, Jianmin; Liu, Weiguo; Chen, Zhe; He, Shuda; Zheng, Shu

    2014-01-01

    Aim of the study To establish and evaluate the fingerprint diagnostic models of cerebrospinal protein profile in glioma with surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) and bioinformatics analysis, in order to seek new tumor markers. Material and methods SELDI-TOF-MS was used to detect the cerebrospinal protein bond to ProteinChip H4. The cerebrospinal protein profiles were obtained and analyzed using the artificial neural network (ANN) method. Fingerprint diagnostic models of cerebrospinal protein profiles for distinguishing glioma from non-brain-tumor, and distinguishing glioma from benign brain tumor, were established. The support vector machine (SVM) algorithm was used for verification of established diagnostic models. The tumor markers were screened. Results In a fingerprint diagnostic model of cerebrospinal protein profiles for distinguishing glioma from non-brain tumor, the sensitivity and specificity of glioma diagnosis were 100% and 91.7%, respectively. Seven candidate tumor markers were obtained. In a fingerprint diagnostic model for distinguishing glioma from benign brain tumor, the sensitivity and specificity of glioma diagnosis were 88.9% and 100%, respectively, and 8 candidate tumor markers were gained. Conclusions The combination of SELDI-TOF-MS and bioinformatics tools is a very effective method for screening and identifying new markers of glioma. The established diagnostic models have provided a new way for clinical diagnosis of glioma, especially for qualitative diagnosis. PMID:24966792

  3. Eikenella corrodens Sepsis with Cerebrospinal Fluid Pleocytosis in a Very Low Birth Weight Neonate

    PubMed Central

    Sawyer, Christopher; Angelis, Dimitrios; Bennett, Robert

    2015-01-01

    We report a case of Eikenella corrodens sepsis associated with CSF pleocytosis in a very low birth weight neonate. A 1000-gram male neonate was born at 27-week gestation due to preterm labor. The patient presented with signs and symptoms of sepsis and was treated for suspected meningitis with intravenous ampicillin and gentamicin for 7 days, with cefotaxime added for three weeks. He had a normal brain MRI at discharge and normal development at 6 months of life. To our knowledge, this is the first case of E. corrodens sepsis and associated meningitis in a very low birth weight neonate. PMID:26635988

  4. The effect of head orientation on subarachnoid cerebrospinal fluid distribution and its implications for neurophysiological modulation and recording techniques.

    PubMed

    Bijsterbosch, Janine D; Lee, Kwang-Hyuk; Hunter, Michael D; Wilkinson, Iain D; Farrow, Tom; Barker, Anthony T; Woodruff, Peter W R

    2013-03-01

    Gravitational forces may lead to local changes in subarachnoid cerebrospinal fluid (CSF) layer thickness, which has important implications for neurophysiological modulation and recording techniques. This study examines the effect of gravitational pull associated with different head positions on the distribution of subarachnoid CSF using structural magnetic resonance imaging. Images of seven subjects in three different positions (supine, left lateral and prone) were statistically compared. Results suggest that subarachnoid CSF volume decreases on the side of the head closest to the ground, due to downward brain movement with gravity. These findings warrant future research into currently unexplored gravitation-induced changes in regional subarachnoid CSF thickness. PMID:23400029

  5. Evaluation of S100B in cerebrospinal fluid as a potential biomarker for neurological diseases in calves

    PubMed Central

    KOJIMA, Yuka; CHIBA, Shiori; HORIUCHI, Noriyuki; KOBAYASHI, Yoshiyasu; INOKUMA, Hisashi

    2015-01-01

    S100B in cerebrospinal fluid (CSF-S100B) was measured in calves with 20 neurologic and 21 non-neurologic diseases to clarify its utility as a biomarker for neurologic diseases. The median CSF-S100B value in the neurologic disease group (43.0 ng/ml) was significantly higher than that in the non-neurologic disease group (10.2 ng/ml). As CSF-S100B levels in calves with neurologic diseases widely differed, the utility of CSF-S100B as a diagnostic marker for neurologic diseases in cattle remains inconclusive. PMID:25649061

  6. Interpretation of high levels of HIV-1 RNA in the cerebrospinal fluid (CSF) using amplicor HIV-1 monitor test.

    PubMed

    Honderlick, P; Zucman, D; Couderc, L J

    1999-05-01

    A retrospective study of 19 cerebrospinal fluid (CSF) specimens from 14 HIV-positive subjects with subacute encephalopathy, neuropathy, or unexplained peripheral myelopathy was done comparatively with plasma specimens collected on the same day and tested in the same run as the corresponding CSF specimen. A single patient had a high HIV RNA level in CSF as compared to plasma (CSF/plasma ratio > 10), which seemed correlated with the clinical course. Further studies are needed to confirm that a high CSF/plasma HIV RNA ratio is associated with greater symptom severity. PMID:10418040

  7. Brain function estimated from the ratio of glutamine to homocarnosine levels in cerebrospinal fluid.

    PubMed

    Ohtsuka, C; Takahashi, H

    1983-01-01

    The ratio of glutamine to homocarnosine (G/H ratio) in CSF of children with meningeal pathology or convulsions was measured and the following results were obtained. 1. The mean G/H ratio of normal subjects was 83.0 +/- 41.4. 2. The mean G/H ratios of the patients with bacterial meningitis and meningeal leukemia were 115.9 +/- 81.9 and 115.2 +/- 49.2, respectively. Significant differences were found between those in normal subjects and these diseases. 3. The mean G/H ratio of the patients with viral meningitis was 80.0 +/- 35.1 and no significant difference was found between normal subjects and these patients. 4. The mean G/H ratios in the patients with controlled versus uncontrolled epilepsy were 130.9 +/- 67.1 and 74.8 +/- 49.4, respectively. A significant difference was found between normal subjects and the patients with controlled epilepsy. 5. The mean G/H ratio in the patients with febrile convulsions was 46.5 +/- 6.3. A significant difference was found between normal subjects and these patients. These data suggest that a high G/H ratio in CSF may indicate the excited state of the brain. PMID:6660425

  8. Distribution in cerebrospinal fluid, blood, and lymph of epidurally injected morphine and inulin in dogs

    SciTech Connect

    Durant, P.A.; Yaksh, T.L.

    1986-06-01

    We describe procedures for catheterizing the epidural space, the azygos vein, and the thoracic lymph duct of dogs without using fluoroscopy. The success rates of the procedures were 100, 80, and 50%, respectively (n = 10). To assess the validity of the model, /sup 3/H-morphine and unlabeled morphine (2 mg) were injected epidurally in ten dogs. Lumbar cerebrospinal fluid (CSF), azygos venous blood, arterial blood, and lymph were sampled before and 5, 20, 60, 120, 180, 240, 300 and 360 min after injection. During the first 20 min, morphine levels in the azygos vein were about three and ten times greater than arterial and lymphatic levels, respectively (n = 3; P less than 0.01). Morphine levels were significantly greater in the azygos vein (n = 8) and the femoral artery (n = 10) during the first 20 and 60 min than they were later, respectively (P less than 0.05). In the lymph (n = 5), the levels of morphine at 60 min were statistically greater (P less than 0.05) than levels at 4, 5, and 6 hr. At no time were the concurrent arterial and lymph levels different from each other. In the lumbar CSF, the morphine peak concentration was reached 5-60 min after epidural injection and ranged between 5 and 93 micrograms/ml. In the CSF, the levels of morphine were significantly greater during the first 20 min than later (n = 7; P less than 0.05). The washout of the lumbar CSF curve for morphine appeared to be fitted by a two-compartment open model. The t1/2-alpha and t1/2-beta values were 14.7 +/- 7.2 min and 106 +/- 45 min, respectively (mean +/- SD). Cumulative percentages of the epidural dose of morphine passed into the azygos system within the first 5, 20, 60, and 120 min after injection were calculated to be 4.0 +/- 2.1, 23.5 +/- 14.6, 49.2 +/- 34.2, and 55.9 +/- 35.3, respectively (mean +/- SD; n = 8).

  9. Dissecting IWG-2 typical and atypical Alzheimer's disease: insights from cerebrospinal fluid analysis.

    PubMed

    Paterson, Ross W; Toombs, Jamie; Slattery, Catherine F; Nicholas, Jennifer M; Andreasson, Ulf; Magdalinou, Nadia K; Blennow, Kaj; Warren, Jason D; Mummery, Cath J; Rossor, Martin N; Lunn, Michael P; Crutch, Sebastian J; Fox, Nick C; Zetterberg, Henrik; Schott, Jonathan M

    2015-12-01

    Pathobiological factors underlying phenotypic diversity in Alzheimer's disease (AD) are incompletely understood. We used an extended cerebrospinal fluid (CSF) panel to explore differences between "typical" with "atypical" AD and between amnestic, posterior cortical atrophy, logopenic aphasia and frontal variants. We included 97 subjects fulfilling International Working Group-2 research criteria for AD of whom 61 had "typical" AD and 36 "atypical" syndromes, and 30 controls. CSF biomarkers included total tau (T-tau), phosphorylated tau (P-tau), amyloid ?1-42, amyloid ?X-38/40/42, YKL-40, neurofilament light (NFL), and amyloid precursor proteins ? and ?. The typical and atypical groups were matched for age, sex, severity and rate of cognitive decline and had similar biomarker profiles, with the exception of NFL which was higher in the atypical group (p = 0.03). Sub-classifying the atypical group into its constituent clinical syndromes, posterior cortical atrophy was associated with the lowest T-tau [604.4 (436.8-675.8) pg/mL], P-tau (79.8 ± 21.8 pg/L), T-tau/A?1-42 ratio [2.3 (1.4-2.6)], A?X-40/X-42 ratio (22.1 ± 5.8) and rate of cognitive decline [1.9 (0.75-4.25) MMSE points/year]. Conversely, the frontal variant group had the highest levels of T-tau [1185.4 (591.7-1329.3) pg/mL], P-tau (116.4 ± 45.4 pg/L), T-tau/A?1-42 ratio [5.2 (3.3-6.9)] and A?X-40/X-42 ratio (27.9 ± 7.5), and rate of cognitive decline. Whilst on a group level IWG-2 "typical" and "atypical" AD share similar CSF profiles, which are very different from controls, atypical AD is a heterogeneous entity with evidence for subtle differences in amyloid processing and neurodegeneration between different clinical syndromes. These findings also have practical implications for the interpretation of clinical CSF biomarker results. PMID:26410752

  10. The cerebrospinal fluid proteome in HIV infection: change associated with disease severity.

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Spudich, Serena S.; Gritsenko, Marina A.; Fuchs, Dietmar; Liegler, Teri; Zetterberg, Henrik; Camp, David G.; Price, Richard W.; Smith, Richard D.

    2012-03-20

    Central nervous system (CNS) infection is a constant feature of systemic HIV infection with a clinical spectrum that ranges from chronic asymptomatic infection to severe cognitive and motor dysfunction. Analysis of cerebrospinal fluid (CSF) has played an important part in defining the character of this evolving infection and response to treatment. To further characterize CNS HIV infection and its effects, we applied advanced high-throughput proteomic methods to CSF to identify novel proteins and their changes with disease progression and treatment. After establishing an accurate mass and time (AMT) tag database containing 23,141 AMT tags for CSF peptides, we analyzed 91 CSF samples by LC-MS from 12 HIV-uninfected and 14 HIV-infected subjects studied in the context of initiation of antiretroviral and correlated abundances of identified proteins (a) within and between subjects, (b) with all other proteins across the entire sample set, and (c) with 'external' CSF biomarkers of infection (HIV RNA), immune activation (neopterin) and neural injury (neurofilament light chain protein, NFL). We identified a mean of 2,333 +/- 328 (SD) peptides covering 307 +/-16 proteins in the 91 CSF sample set. Protein abundances differed both between and within subjects sampled at different time points and readily separated those with and without HIV infection. Proteins also showed inter-correlations across the sample set that were associated with biologically relevant dynamic processes. One-hundred and fifty proteins showed correlations with the external biomarkers. For example, using a threshold of cross correlation coefficient (Pearson's) {le}0.3 and {ge}0.3 for potentially meaningful relationships, a total of 99 proteins correlated with CSF neopterin (43 negative and 56 positive correlations) and related principally to neuronal plasticity and survival and to innate immunity. Pathway analysis defined several networks connecting the identified proteins, including one with amyloid precursor protein as a central node. Advanced CSF proteomic analysis enabled the identification of an array of novel protein changes across the spectrum of CNS HIV infection and disease. This initial analysis clearly demonstrated the value of contemporary state-of-the-art proteomic CSF analysis as a discovery tool in HIV infection with likely similar application to other neurological inflammatory and degenerative diseases.

  11. Cerebrospinal Fluid P-Tau181P: Biomarker for Improved Differential Dementia Diagnosis

    PubMed Central

    Struyfs, Hanne; Niemantsverdriet, Ellis; Goossens, Joery; Fransen, Erik; Martin, Jean-Jacques; De Deyn, Peter P.; Engelborghs, Sebastiaan

    2015-01-01

    The goal of this study is to investigate the value of tau phosphorylated at threonine 181 (P-tau181P) in the Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarker panel for differential dementia diagnosis in autopsy confirmed AD and non-AD patients. The study population consisted of 140 autopsy confirmed AD and 77 autopsy confirmed non-AD dementia patients. CSF concentrations of amyloid-? peptide of 42 amino acids (A?1–42), total tau protein (T-tau), and P-tau181P were determined with single analyte ELISA-kits (INNOTEST®, Fujirebio, Ghent, Belgium). Diagnostic accuracy was assessed through receiver operating characteristic (ROC) curve analyses to obtain area under the curve (AUC) values and to define optimal cutoff values to discriminate AD from pooled and individual non-AD groups. ROC curve analyses were only performed on biomarkers and ratios that differed significantly between the groups. Pairwise comparison of AUC values was performed by means of DeLong tests. The A?1–42/P-tau181P ratio (AUC?=?0.770) performed significantly better than A?1–42 (AUC?=?0.677, P?=?0.004), T-tau (AUC?=?0.592, P?

  12. Cerebrospinal Fluid Biomarker and Brain Biopsy Findings in Idiopathic Normal Pressure Hydrocephalus

    PubMed Central

    Pyykkö, Okko T.; Lumela, Miikka; Rummukainen, Jaana; Nerg, Ossi; Seppälä, Toni T.; Herukka, Sanna-Kaisa; Koivisto, Anne M.; Alafuzoff, Irina; Puli, Lakshman; Savolainen, Sakari; Soininen, Hilkka; Jääskeläinen, Juha E.; Hiltunen, Mikko; Zetterberg, Henrik; Leinonen, Ville

    2014-01-01

    Background The significance of amyloid precursor protein (APP) and neuroinflammation in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) is unknown. Objective To investigate the role of soluble APP (sAPP) and amyloid beta (A?) isoforms, proinflammatory cytokines, and biomarkers of neuronal damage in the cerebrospinal fluid (CSF) in relation to brain biopsy A? and hyperphosphorylated tau (HP?) findings. Methods The study population comprised 102 patients with possible NPH with cortical brain biopsies, ventricular and lumbar CSF samples, and DNA available. The final clinical diagnoses were: 53 iNPH (91% shunt-responders), 26 AD (10 mixed iNPH+AD), and 23 others. Biopsy samples were immunostained against A? and HP?. CSF levels of AD-related biomarkers (A?42, p-tau, total tau), non-AD-related A? isoforms (A?38, A?40), sAPP isoforms (sAPP?, sAPP?), proinflammatory cytokines (several interleukins (IL), interferon-gamma, monocyte chemoattractant protein-1, tumor necrosis factor-alpha) and biomarkers of neuronal damage (neurofilament light and myelin basic protein) were measured. All patients were genotyped for APOE. Results Lumbar CSF levels of sAPP? were lower (p<0.05) in patients with shunt-responsive iNPH compared to non-iNPH patients. sAPP? showed a similar trend (p?=?0.06). CSF sAPP isoform levels showed no association to A? or HP? in the brain biopsy. Quantified A? load in the brain biopsy showed a negative correlation with CSF levels of A?42 in ventricular (r?=??0.295, p?=?0.003) and lumbar (r?=??0.356, p?=?0.01) samples, while the levels of A?38 and A?40 showed no correlation. CSF levels of proinflammatory cytokines and biomarkers of neuronal damage did not associate to the brain biopsy findings, diagnosis, or shunt response. Higher lumbar/ventricular CSF IL-8 ratios (p<0.001) were seen in lumbar samples collected after ventriculostomy compared to the samples collected before the procedure. Conclusions The role of sAPP isoforms in iNPH seems to be independent from the amyloid cascade. No neuroinflammatory background was observed in iNPH or AD. PMID:24638077

  13. Cerebrospinal fluid peptides as potential Parkinson disease biomarkers: a staged pipeline for discovery and validation.

    PubMed

    Shi, Min; Movius, James; Dator, Romel; Aro, Patrick; Zhao, Yanchun; Pan, Catherine; Lin, Xiangmin; Bammler, Theo K; Stewart, Tessandra; Zabetian, Cyrus P; Peskind, Elaine R; Hu, Shu-Ching; Quinn, Joseph F; Galasko, Douglas R; Zhang, Jing

    2015-03-01

    Finding robust biomarkers for Parkinson disease (PD) is currently hampered by inherent technical limitations associated with imaging or antibody-based protein assays. To circumvent the challenges, we adapted a staged pipeline, starting from our previous proteomic profiling followed by high-throughput targeted mass spectrometry (MS), to identify peptides in human cerebrospinal fluid (CSF) for PD diagnosis and disease severity correlation. In this multicenter study consisting of training and validation sets, a total of 178 subjects were randomly selected from a retrospective cohort, matching age and sex between PD patients, healthy controls, and neurological controls with Alzheimer disease (AD). From ?14,000 unique peptides displaying differences between PD and healthy control in proteomic investigations, 126 peptides were selected based on relevance and observability in CSF using bioinformatic analysis and MS screening, and then quantified by highly accurate and sensitive selected reaction monitoring (SRM) in the CSF of 30 PD patients versus 30 healthy controls (training set), followed by diagnostic (receiver operating characteristics) and disease severity correlation analyses. The most promising candidates were further tested in an independent cohort of 40 PD patients, 38 AD patients, and 40 healthy controls (validation set). A panel of five peptides (derived from SPP1, LRP1, CSF1R, EPHA4, and TIMP1) was identified to provide an area under curve (AUC) of 0.873 (sensitivity = 76.7%, specificity = 80.0%) for PD versus healthy controls in the training set. The performance was essentially confirmed in the validation set (AUC = 0.853, sensitivity = 82.5%, specificity = 82.5%). Additionally, this panel could also differentiate the PD and AD groups (AUC = 0.990, sensitivity = 95.0%, specificity = 97.4%). Furthermore, a combination of two peptides belonging to proteins TIMP1 and APLP1 significantly correlated with disease severity as determined by the Unified Parkinson's Disease Rating Scale motor scores in both the training (r = 0.381, p = 0.038)j and the validation (r = 0.339, p = 0.032) sets. The novel panel of CSF peptides, if validated in independent cohorts, could be used to assist in clinical diagnosis of PD and has the potential to help monitoring or predicting disease progression. PMID:25556233

  14. Disease Biomarkers in Cerebrospinal Fluid of Patients with First-Onset Psychosis

    PubMed Central

    Oxley, David; Wang, Lan; Harris, Nathan; Koethe, Dagmar; Gerth, Christoph W; Nolden, Brit M; Gross, Sonja; Schreiber, Daniela; Reed, Benjamin; Bahn, Sabine

    2006-01-01

    Background Psychosis is a severe mental condition that is characterized by a loss of contact with reality and is typically associated with hallucinations and delusional beliefs. There are numerous psychiatric conditions that present with psychotic symptoms, most importantly schizophrenia, bipolar affective disorder, and some forms of severe depression referred to as psychotic depression. The pathological mechanisms resulting in psychotic symptoms are not understood, nor is it understood whether the various psychotic illnesses are the result of similar biochemical disturbances. The identification of biological markers (so-called biomarkers) of psychosis is a fundamental step towards a better understanding of the pathogenesis of psychosis and holds the potential for more objective testing methods. Methods and Findings Surface-enhanced laser desorption ionization mass spectrometry was employed to profile proteins and peptides in a total of 179 cerebrospinal fluid samples (58 schizophrenia patients, 16 patients with depression, five patients with obsessive-compulsive disorder, ten patients with Alzheimer disease, and 90 controls). Our results show a highly significant differential distribution of samples from healthy volunteers away from drug-naïve patients with first-onset paranoid schizophrenia. The key alterations were the up-regulation of a 40-amino acid VGF-derived peptide, the down-regulation of transthyretin at ~4 kDa, and a peptide cluster at ~6,800–7,300 Da (which is likely to be influenced by the doubly charged ions of the transthyretin protein cluster). These schizophrenia-specific protein/peptide changes were replicated in an independent sample set. Both experiments achieved a specificity of 95% and a sensitivity of 80% or 88% in the initial study and in a subsequent validation study, respectively. Conclusions Our results suggest that the application of modern proteomics techniques, particularly mass spectrometric approaches, holds the potential to advance the understanding of the biochemical basis of psychiatric disorders and may in turn allow for the development of diagnostics and improved therapeutics. Further studies are required to validate the clinical effectiveness and disease specificity of the identified biomarkers. PMID:17090210

  15. Identification and Validation of Novel Cerebrospinal Fluid Biomarkers for Staging Early Alzheimer's Disease

    PubMed Central

    Malone, James P.; Shah, Aarti R.; Gilmore, Petra; Davis, Alan E.; Roe, Catherine M.; Peskind, Elaine R.; Li, Ge; Galasko, Douglas R.; Clark, Christopher M.; Quinn, Joseph F.; Kaye, Jeffrey A.; Morris, John C.; Holtzman, David M.; Townsend, R. Reid; Fagan, Anne M.

    2011-01-01

    Background Ideally, disease modifying therapies for Alzheimer disease (AD) will be applied during the ‘preclinical’ stage (pathology present with cognition intact) before severe neuronal damage occurs, or upon recognizing very mild cognitive impairment. Developing and judiciously administering such therapies will require biomarker panels to identify early AD pathology, classify disease stage, monitor pathological progression, and predict cognitive decline. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid (CSF) proteome. Methods and Findings CSF samples from individuals with mild AD (Clinical Dementia Rating [CDR] 1) (n?=?24) and cognitively normal controls (CDR 0) (n?=?24) were subjected to two-dimensional difference-in-gel electrophoresis. Within 119 differentially-abundant gel features, mass spectrometry (LC-MS/MS) identified 47 proteins. For validation, eleven proteins were re-evaluated by enzyme-linked immunosorbent assays (ELISA). Six of these assays (NrCAM, YKL-40, chromogranin A, carnosinase I, transthyretin, cystatin C) distinguished CDR 1 and CDR 0 groups and were subsequently applied (with tau, p-tau181 and A?42 ELISAs) to a larger independent cohort (n?=?292) that included individuals with very mild dementia (CDR 0.5). Receiver-operating characteristic curve analyses using stepwise logistic regression yielded optimal biomarker combinations to distinguish CDR 0 from CDR>0 (tau, YKL-40, NrCAM) and CDR 1 from CDR<1 (tau, chromogranin A, carnosinase I) with areas under the curve of 0.90 (0.85–0.94 95% confidence interval [CI]) and 0.88 (0.81–0.94 CI), respectively. Conclusions Four novel CSF biomarkers for AD (NrCAM, YKL-40, chromogranin A, carnosinase I) can improve the diagnostic accuracy of A?42 and tau. Together, these six markers describe six clinicopathological stages from cognitive normalcy to mild dementia, including stages defined by increased risk of cognitive decline. Such a panel might improve clinical trial efficiency by guiding subject enrollment and monitoring disease progression. Further studies will be required to validate this panel and evaluate its potential for distinguishing AD from other dementing conditions. PMID:21264269

  16. Cerebrospinal fluid kynurenines in multiple sclerosis; relation to disease course and neurocognitive symptoms.

    PubMed

    Aeinehband, Shahin; Brenner, Philip; Ståhl, Sara; Bhat, Maria; Fidock, Mark D; Khademi, Mohsen; Olsson, Tomas; Engberg, Göran; Jokinen, Jussi; Erhardt, Sophie; Piehl, Fredrik

    2016-01-01

    Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, with a high rate of neurocognitive symptoms for which the molecular background is still uncertain. There is accumulating evidence for dysregulation of the kynurenine pathway (KP) in different psychiatric and neurodegenerative conditions. We here report the first comprehensive analysis of cerebrospinal fluid (CSF) kynurenine metabolites in MS patients of different disease stages and in relation to neurocognitive symptoms. Levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) were determined with liquid chromatography mass spectrometry in cell-free CSF. At the group level MS patients (cohort 1; n=71) did not differ in absolute levels of TRP, KYN, KYNA or QUIN as compared to non-inflammatory neurological disease controls (n=20). Stratification of patients into different disease courses revealed that both absolute QUIN levels and the QUIN/KYN ratio were increased in relapsing-remitting MS (RRMS) patients in relapse. Interestingly, secondary progressive MS (SPMS) displayed a trend for lower TRP and KYNA, while primary progressive (PPMS) patients displayed increased levels of all metabolites, similar to a group of inflammatory neurological disease controls (n=13). In the second cohort (n=48), MS patients with active disease and short disease duration were prospectively evaluated for neuropsychiatric symptoms. In a supervised multivariate analysis using orthogonal projection to latent structures (OPLS-DA) depressed patients displayed higher KYNA/TRP and KYN/TRP ratios, mainly due to low TRP levels. Still, this model had low predictive value and could not completely separate the clinically depressed patients from the non-depressed MS patients. No correlation was evident for other neurocognitive measures. Taken together these results demonstrate that clinical disease activity and differences in disease courses are reflected by changes in KP metabolites. Increased QUIN levels of RRMS patients in relapse and generally decreased levels of TRP in SPMS may relate to neurotoxicity and failure of remyelination, respectively. In contrast, PPMS patients displayed a more divergent pattern more resembling inflammatory conditions such as systemic lupus erythematosus. The pattern of KP metabolites in RRMS patients could not predict neurocognitive symptoms. PMID:26189678

  17. A diagnostic scale for Alzheimer’s disease based on cerebrospinal fluid biomarker profiles

    PubMed Central

    2014-01-01

    Introduction The relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer’s disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer’s disease (AD) pathologic process. Methods For that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-? 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included. Results A prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale’s overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent multicenter dataset of 408 patients (213 AD and 195 non-AD). Conclusions In conclusion, we defined a new scale that could be used to facilitate the interpretation and routine use of multivariate CSF data, as well as helping the stratification of patients in clinical research trials. PMID:25478015

  18. Selenium speciation in paired serum and cerebrospinal fluid samples of sheep.

    PubMed

    Humann-Ziehank, Esther; Ganter, Martin; Michalke, Bernhard

    2016-01-01

    This study was performed to characterise selenium (Se) and Se species in cerebrospinal fluid (CSF) of sheep and its relation to the respective Se concentrations in serum. Paired samples from 10 adult sheep were used for the study. Five sheep were fed a diet with a marginal Se concentration of <0.05mg Se/kg diet dry weight (dw, Se(-)), and five animals were fed the same diet supplemented with sodium selenite revealing a concentration of 0.2mg Se/kg diet dw (Se(+)). The feeding strategy was conducted for two years; The results on metabolic effects were published previously. At the end of the feeding period, paired samples of serum and CSF were collected and analysed using ion exchange chromatography inductively coupled plasma-dynamic reaction cell-mass spectrometry (IEC-ICP-DRC-MS) technique for total Se concentration and concentrations of Se species. Albumin concentrations were analysed additionally. The feeding strategy caused significant differences (p<0.01) in serum Se concentrations with 33.1±5.11?g Se/l in the Se(-) group and 96.5±18.3?g Se/l in the Se(+) group, respectively. The corresponding total Se concentrations in CSF were 4.38±1.02?g Se/l and 6.13±1.64?g Se/l in the Se(-) and the Se(+) group, respectively, missing statistical significance (p=0.077). IEC-ICP-DRC-MS technique was able to differentiate the Se species selenoprotein P-bound Se (SePP), selenomethionine, glutathione peroxidase-bound Se (Se-GPx), selenocystine, thioredoxin reductase-bound Se, ovine serum albumin-bound Se (Se-OSA), SeIV and SeVI in ovine serum and CSF. Quantitatively, SePP is the main selenoprotein in ovine serum followed by Se-GPx. The CSF/blood ratio of albumin (QAlbumin) reflected a physiological function of the blood-CSF barrier in all sheep. QSe-species were higher than QAlbumin both feeding groups, supporting the hypothesis of local production of Se species in the brain. Significant positive regression lines for CSF vs. serum were found for albumin and Se-OSA only, suggesting a role of albumin to convey Se across the blood-CSF barrier. The ovine model, together with the IEC-ICP-DRC-MS technique to characterise the Se species, might be a worthwhile model for further studies as repeated sample collection as well as modification of the nutritional status is feasible and effective. PMID:26653738

  19. Human Parasitic Meningitis Caused by Angiostrongylus cantonensis Infection in Taiwan

    PubMed Central

    Chen, Yao-Shen; Yen, Chuan-Min

    2013-01-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophlic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection. PMID:23901378

  20. Human parasitic meningitis caused by Angiostrongylus cantonensis infection in Taiwan.

    PubMed

    Tsai, Hung-Chin; Chen, Yao-Shen; Yen, Chuan-Min

    2013-06-01

    The major cause of eosinophilic meningitis in Taiwan is Angiostrongylus cantonensis. Humans are infected by ingesting terrestrial and freshwater snails and slugs. In 1998 and 1999, two outbreaks of eosinophilic meningitis caused by A. cantonensis infection were reported among 17 adult male immigrant Thai laborers who had eaten raw golden apple snails (Pomacea canaliculata). Another outbreak associated with consuming a health drink consisting of raw vegetable juice was reported in 2001. These adult cases differed from reports in the 1970s and 1980s, in which most of the cases were in children. With improvements in public health and education of foreign laborers, there have since been only sporadic cases in Taiwan. Review of clinical research indicates inconsistent association of Magnetic Resonance Imaging (MRI) results with clinical features of eosinophilic meningitis. MRI features were nonspecific but there was an association between the presence of high brain MRI signal intensities and severity of peripheral and cerebrospinal fluid (CSF) eosinophilia. Inflammatory markers have been identified in the CSF of patients with eosinophilic meningitis caused by A. cantonensis infection, and vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and the matrix metalloproteinase system may be associated with blood-brain barrier disruption. Eosinophilic meningitis caused by A. cantonensis infection is not a reportable disease in Taiwan. It is important that a public advisory and education program be developed to reduce future accidental infection. PMID:23901378

  1. Estimation of the Lateral Ventricles Volumes from a 2D Image and Its Relationship with Cerebrospinal Fluid Flow

    PubMed Central

    Bader, Chaarani; Cyrille, Capel; Jadwiga, Zmudka; Joel, Daouk; Fichten, Anthony; Catherine, Gondry-Jouet; Roger, Bouzerar; Olivier, Balédent

    2013-01-01

    Purpose. This work suggests a fast estimation method of the lateral ventricles volume from a 2D image and then determines if this volume is correlated with the cerebrospinal fluid flow at the aqueductal and cerebral levels in neurodegenerative diseases. Materials and Methods. FForty-five elderly patients suffering from Alzheimer's disease (19), normal pressure hydrocephalus (13), and vascular dementia (13) were involved and underwent anatomical and phase contrast MRI scans. Lateral ventricles and stroke volumes were assessed on anatomical and phase contrast scans, respectively. A common reference plane was used to calculate the lateral ventricles' area on 2D images. Results. The largest volumes were observed in hydrocephalus patients. The linear regression between volumes and areas was computed, and a strong positive correlation was detected (R2 = 0.9). A derived equation was determined to represent the volumes for any given area. On the other hand, no significant correlations were detected between ventricles and stroke volumes (R2 ? 0.15). Conclusion. Lateral ventricles volumes are significantly proportional to the 2D reference section area and could be used for patients' follow-up even if 3D images are unavailable. The cerebrospinal fluid fluctuations in brain disorders may depend on many physiological parameters other than the ventricular morphology. PMID:24151585

  2. Delayed cerebrospinal fluid sterilization, in vitro bactericidal activities, and side effects of selected beta-lactams.

    PubMed

    Dajani, A S; Pokowski, L H

    1990-01-01

    Ampicillin (or penicillin G) plus chloramphenicol, cefuroxime, ceftriaxone, and cefotaxime have been used in the treatment of bacterial meningitis beyond the neonatal period. Review of recent data from the USA and Europe indicates that delayed CSF sterilization occurs significantly more often with ampicillin/chloramphenicol and cefuroxime than with ceftriaxone and cefotaxime. Delayed CSF sterilization is associated with an increased morbidity and neurological complications. Previously reported in vitro interactions between chloramphenicol and various beta-lactam antibiotics indicate that for bacteria where chloramphenicol is only bacteriostatic, the combination of chloramphenicol with beta-lactams is antagonistic. Killing rates of various beta-lactams were compared against a number of gram-positive and gram-negative bacteria. Cidal activity of some beta-lactams was inoculum dependent. There was a good correlation between in vitro activity and ability to sterilize CSF. Ceftriaxone is highly protein bound and its use in newborns is discouraged. Diarrhea occurs significantly more often after cefriaxone use than after the use of other agents. Ceftriaxone is uniquely associated with a high frequency of biliary pseudolithiasis which may be symptomatic and can cause measureable morbidity. In selecting the "proper" antimicrobial agent for the treatment of bacterial meningitis considerations should be given to proven clinical efficacy, prompt CSF sterilization, rapid in vitro cidal activity, safety and cost. We recommend cefotaxime as the agent of choice in the treatment of bacterial meningitis. PMID:2091255

  3. Human Parechovirus 3 Meningitis and Fatal Leukoencephalopathy.

    PubMed

    Bissel, Stephanie J; Auer, Roland N; Chiang, Cheng-Hsuan; Kofler, Julia; Murdoch, Geoffrey H; Nix, W Allan; Painter, Michael; Richer, Maxime; Sartelet, Hervé; Wang, Guoji; Wiley, Clayton A

    2015-08-01

    Human parechovirus 3 (HPeV3) is a picornavirus associated with neurologic disease in neonates. Human parechovirus 3 infection of preterm and term infants is associated with seizures and destructive periventricular white matter lesions. Despite unremarkable cerebrospinal fluid (CSF), HPeV3 RNA can be amplified from CSF and nasopharyngeal and rectal swabs. We report pathologic findings in 2 autopsy cases of infants with active HPeV3 infection. Both children were born approximately 1 month premature and were neurologically intact but, after a few weeks, developed seizures and radiologic evidence of white matter lesions. Neuropathologic examination demonstrated classic severe periventricular leukomalacia in the absence of an immune response. Human parechovirus 3 sequences were identified in RNA extracted from CSF, sera, and tissues. Human parechovirus 3 in situ hybridization detection of infected cells was limited to meninges and associated blood vessels in addition to smooth muscle of pulmonary vessels. Ultrastructural evaluation of meninges demonstrated dense core structures compatible with picornavirus virions. These findings suggest that encephalopathic changes are secondary to infection of meninges and potential compromise of vascular perfusion. Thus, parechovirus infection of vascular smooth muscle may be a more general pathogenic process. PMID:26115191

  4. Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age

    PubMed Central

    Sutphen, Courtney L.; Jasielec, Mateusz S.; Shah, Aarti R.; Macy, Elizabeth M.; Xiong, Chengjie; Vlassenko, Andrei G.; Benzinger, Tammie L. S.; Stoops, Erik E. J.; Vanderstichele, Hugo M. J.; Brix, Britta; Darby, Heather D.; Vandijck, Manu L. J.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.; Fagan, Anne M.

    2015-01-01

    IMPORTANCE Individuals in the presymptomatic stage of Alzheimer disease (AD) are increasingly being targeted for AD secondary prevention trials. How early during the normal life span underlying AD pathologies begin to develop, their patterns of change over time, and their relationship with future cognitive decline remain to be determined. OBJECTIVE To characterize the within-person trajectories of cerebrospinal fluid (CSF) biomarkers of AD over time and their association with changes in brain amyloid deposition and cognitive decline in cognitively normal middle-aged individuals. DESIGN, SETTING, AND PARTICIPANTS As part of a cohort study, cognitively normal (Clinical Dementia Rating [CDR] of 0) middle-aged research volunteers (n = 169) enrolled in the Adult Children Study at Washington University, St Louis, Missouri, had undergone serial CSF collection and longitudinal clinical assessment (mean, 6 years; range, 0.91–11.3 years) at 3-year intervals at the time of analysis, between January 2003 and November 2013. A subset (n = 74) had also undergone longitudinal amyloid positron emission tomographic imaging with Pittsburgh compound B (PiB) in the same period. Serial CSF samples were analyzed for ?-amyloid 40 (A?40), A?42, total tau, tau phosphorylated at threonine 181 (P-tau181), visinin-like protein 1 (VILIP-1), and chitinase-3-like protein 1 (YKL-40). Within-person measures were plotted according to age and AD risk defined by APOE genotype (?4 carriers vs noncarriers). Linear mixed models were used to compare estimated biomarker slopes among middle-age bins at baseline (early, 45–54 years; mid, 55–64 years; late, 65–74 years) and between risk groups. Within-person changes in CSF biomarkers were also compared with changes in cortical PiB binding and progression to a CDR higher than 0 at follow-up. MAIN OUTCOMES AND MEASURES Changes in A?40, A?42, total tau, P-tau181, VILIP-1, and YKL-40 and, in a subset of participants, changes in cortical PiB binding. RESULTS While there were no consistent longitudinal patterns in A?40 (P = .001–.97), longitudinal reductions in A?42 were observed in some individuals as early as early middle age (P ? .05) and low A?42 levels were associated with the development of cortical PiB-positive amyloid plaques (area under receiver operating characteristic curve = 0.9352; 95% CI, 0.8895–0.9808), especially in mid middle age (P < .001). Markers of neuronal injury (total tau, P-tau181, and VILIP-1) dramatically increased in some individuals in mid and late middle age (P ? .02), whereas the neuroinflammation marker YKL-40 increased consistently throughout middle age (P ? .003). These patterns were more apparent in at-risk ?4 carriers (A?42 in an allele dose-dependent manner) and appeared to be associated with future cognitive deficits as determined by CDR. CONCLUSIONS AND RELEVANCE Longitudinal CSF biomarker patterns consistent with AD are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline. Such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline. PMID:26147946

  5. Neurogranin as a Cerebrospinal Fluid Biomarker for Synaptic Loss in Symptomatic Alzheimer Disease

    PubMed Central

    Kester, Maartje I.; Teunissen, Charlotte E.; Crimmins, Daniel L.; Herries, Elizabeth M.; Ladenson, Jack. H.; Scheltens, Philip; van der Flier, Wiesje M.; Morris, John C.; Holtzman, David M.; Fagan, Anne M.

    2015-01-01

    IMPORTANCE Neurogranin (NGRN) seems to be a promising novel cerebrospinal fluid (CSF) biomarker for synaptic loss; however, clinical, and especially longitudinal, data are sparse. OBJECTIVE To examine the utility of NGRN, with repeated CSF sampling, for diagnosis, prognosis, and monitoring of Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS Longitudinal study of consecutive patients who underwent 2 lumbar punctures between the beginning of 1995 and the end of 2010 within the memory clinic–based Amsterdam Dementia Cohort. The study included 163 patients: 37 cognitively normal participants (mean [SE] age, 64 [2] years; 38% female; and mean [SE] Mini-Mental State Examination [MMSE] score, 28 [0.3]), 61 patients with mild cognitive impairment (MCI) (mean [SE] age, 68 [1] years; 38% female; and mean [SE] MMSE score, 27 [0.3]), and 65 patients with AD (mean [SE] age, 65 [1] years; 45% female; and mean [SE] MMSE score, 22 [0.7]). The mean (SE) interval between lumbar punctures was 2.0 (0.1) years, and the mean (SE) duration of cognitive follow-up was 3.8 (0.2) years. Measurements of CSF NGRN levels were obtained in January and February 2014. MAIN OUTCOME AND MEASURE Levels of NGRN in CSF samples. RESULTS Baseline CSF levels of NGRN in patients with AD (median level, 2381 pg/mL [interquartile range, 1651-3416 pg/mL]) were higher than in cognitively normal participants (median level, 1712 pg/mL [interquartile range, 1206-2724 pg/mL]) (P = .04). Baseline NGRN levels were highly correlated with total tau and tau phosphorylated at threonine 181 in all patient groups (all P < .001), but not with A?42. Baseline CSF levels of NGRN were also higher in patients with MCI who progressed to AD (median level, 2842 pg/mL [interquartile range, 1882-3950 pg/mL]) compared with those with stable MCI (median level, 1752 pg/mL [interquartile range, 1024-2438 pg/mL]) (P = .004), and they were predictive of progression from MCI to AD (hazard ratio, 1.8 [95% CI, 1.1-2.9]; stratified by tertiles). Linear mixed-model analyses demonstrated that within-person levels of NGRN increased over time in cognitively normal participants (mean [SE] level, 90 [45] pg/mL per year; P < .05) but not in patients with MCI or AD. CONCLUSIONS AND RELEVANCE Neurogranin is a promising biomarker for AD because levels were elevated in patients with AD compared with cognitively normal participants and predicted progression from MCI to AD. Within-person levels of NGRN increased in cognitively normal participants but not in patients with later stage MCI or AD, which suggests that NGRN may reflect presymptomatic synaptic dysfunction or loss. PMID:26366630

  6. Childhood Psychosis and Monoamine Metabolites in Spinal Fluid.

    ERIC Educational Resources Information Center

    Gillberg, Christopher; And Others

    1983-01-01

    Analysis of cerebrospinal fluid of 22 psychotic children, 22 normal controls, and Ss with mental retardation, progressive encephalopathy, or meningitis revealed that psychotic Ss had raised levels of homovanillic acid. Thirteen Ss diagnosed as autistic showed isolated inrease of this metabolite. Increased concentration of mongamines was not…

  7. Successful lumbar puncture with Taylor's approach for the diagnostic workup of meningitis in a patient with Ankylosing spondylitis

    PubMed Central

    Shrestha, Gentle Sunder; Acharya, Subhash Prasad; Keyal, Niraj; Paneru, Hem Raj; Shrestha, Pramesh Sunder

    2015-01-01

    Meningitis and encephalitis are the neurological emergencies. As the clinical findings lack specificity, once suspected, cerebrospinal fluid (CSF) analysis should be performed and parenteral antimicrobials should be administered without delay. Lumbar puncture can be technically challenging in patients with ankylosing spondylitis due to ossification of ligaments and obliteration of interspinous spaces. Here, we present a case of ankylosing spondylitis where attempts for lumbar puncture by conventional approach failed. CSF sample was successfully obtained by Taylor's approach. PMID:26628829

  8. Analysis of clinical information and reverse transcriptase-polymerase chain reaction for early diagnosis of enteroviral meningitis

    PubMed Central

    Jin, Dahee; Heo, Tae Hoon; Byeon, Jung Hye; Kim, Gun-Ha; Kim, Mi Kyung; Eun, So-Hee

    2015-01-01

    Purpose Meningitis is among the most common infections affecting the central nervous system. It can be difficult to determine the exact pathogen responsible for the infection and patients are often treated with empiric antibiotics. This study was conducted to identify the most common clinical characteristics of enteroviral meningitis in children and evaluate the diagnostic efficacy of reverse transcriptase-polymerase chain reaction (RT-PCR) for early detection of an enterovirus. Methods We analyzed the medical records of children admitted to Korea University Medical Center and diagnosed with meningitis on the basis of cerebrospinal fluid (CSF) analysis and RT-PCR from CSF and other samples from January 2010 to August 2013. Results A total of 333 patients were enrolled and classified into four groups based on diagnosis: enteroviral meningitis (n=110), bacterial meningitis (n=23), other viral meningitis (n=36), and unknown etiology (n=164). Patients with bacterial meningitis were younger than those in the other groups (P<0.001). Pleocytosis in CSF was similar across all groups. Of patients in the enteroviral meningitis group, 92.7% were diagnosed based on RT-PCR findings. Mean length of hospital stay for patients with enteroviral meningitis was 6.08 days, which was significantly shorter than that for patients with meningitis of bacterial etiology (19.73 days, P<0.001). Conclusion Diagnosis of enteroviral meningitis before viral culture results are available is possible using RT-PCR. Accurate diagnosis reduces the length of hospital stay and helps to avoid unnecessary empiric antibiotic treatment. PMID:26692881

  9. Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety of meropenem for adult bacterial meningitis in Japan.

    PubMed

    Morita, Akihiko; Kamei, Satoshi; Minami, Masayuki; Yoshida, Kazuto; Kawabata, Satoshi; Kuroda, Hiroshi; Suzuki, Yasushi; Araki, Nobuo; Iwasaki, Yasuo; Kobayashi, Rei; Hayashi, Naoki; Hirayama, Tetsuyuki; Ochiai, Jun; Ueda, Miki; Yamagishi, Yuka; Niwa, Jun-ichi; Shindo, Katsuro; Fukushima, Yoshihisa; Takita, Tomohiro; Sato, Takayuki; Sato, Shigeru; Mikamo, Hiroshige; Iwata, Satoshi

    2014-09-01

    The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 ?g/ml up to 8.47 h and was over 1 ?g/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens. PMID:24882451

  10. Leuconostoc sp. Meningitis in a Patient Treated with Rituximab for Mantle Cell Lymphoma.

    PubMed

    Holik, Hrvoje; Coha, Božena; Šiško, Marijan; Tomi?-Paradžik, Maja

    2015-09-01

    We present a 64-year-old man who was treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for mantle cell lymphoma and developed purulent meningitis, probably caused by Leuconostoc sp. The patient had severe hypogammaglobulinemia, which is a possible complication of rituximab therapy. To our knowledge and after reviewing the available medical literature, this is the first described case of purulent meningitis caused by Leuconostoc sp. in a patient with mantle cell lymphoma that appeared after treatment with the R-CHOP protocol. The diagnosis of purulent meningitis was based on clinical, laboratory and cytological cerebrospinal fluid findings, in addition to blood culture results in which we isolated Leuconostoc sp. The patient was treated with meropenem with full recovery. PMID:26376594

  11. [A patient with advanced breast cancer who developed bacterial meningitis after chemotherapy].

    PubMed

    Shibata, Kenichi; Suzuki, Akihiko; Suzuki, Takefumi; Sato, Tamie; Yamagishi, Takehito; Kimura, Seishi; Kimura, Wataru

    2014-06-01

    A 76-year-old woman was admitted to our hospital because of a right breast tumor and a skin ulcer. The patient was diagnosed as having advanced breast cancer T4bN2M1(lung), Stage IV. A regimen of 5-fluorouracil(500mg/m2)with epirubicin(100mg/m / 2)and cyclophosphamide(500mg/m2)(FEC100)was administered. However, the patient was hospitalized 12 days later because of febrile neutropenia. The patient experienced a stiff neck the next day, and bacterial meningitis was diagnosed on the basis of cerebrospinal fluid examination. Antibacterial agents were administered according to the clinical practice guidelines of bacterial meningitis. The patient recovered and was discharged from our hospital 24 days after admission. Bacterial meningitis after chemotherapy is rare, but this could be progress to a serious condition. Early diagnosis and treatment are paramount in such cases. PMID:25129092

  12. Meningitis Caused by Streptococcus suis: Case Report and Review of the Literature

    PubMed Central

    Choi, Seong-Min; Cho, Bang-Hoon; Choi, Kang-Ho; Nam, Tai-Seung; Kim, Joon-Tae; Park, Man-Seok; Kim, Myeong-Kyu; Cho, Ki-Hyun

    2012-01-01

    Background Human infection with Streptococcus suis (S. suis), a zoonotic pathogen, has been reported mainly in pig-rearing and pork-consuming countries. Meningitis is the most-common clinical manifestation and is often associated with deafness and vestibular dysfunction. Case Report A 57-year-old man was referred to the hospital with headaches, fevers, chills, and hearing impairment. Meningitis was confirmed and S. suis was isolated from the cerebrospinal fluid. Spondylodiscitis occurred after 2 weeks of antibiotic treatment, and was successfully treated with a prolonged course of antibiotics for another 4 weeks. His hearing loss was irreversible despite the improvement of other symptoms. Conclusions We report the first human case of S. suis infection in Korea. In patients presenting with meningitis, S. suis should be considered if the characteristic features of prominent and early hearing loss are present. PMID:22523518

  13. Biomarkers of Brain Damage: S100B and NSE Concentrations in Cerebrospinal Fluid—A Normative Study

    PubMed Central

    Hajduková, Lenka; Sobek, Ond?ej; Prchalová, Darina; Bílková, Zuzana; Koudelková, Martina; Lukášková, Ji?ina; Matuchová, Inka

    2015-01-01

    NSE and S100B belong among the so-called structural proteins of the central nervous system (CNS). Lately, this group of structural proteins has been profusely used as specific biomarkers of CNS tissue damage. So far, the majority of the research papers have focused predominantly on the concentrations of these proteins in blood in relation to CNS damage of various origins. Considering the close anatomic and functional relationship between the brain or spinal cord and cerebrospinal fluid (CSF), in case of a CNS injury, a rapid and pronounced increase of the concentrations of structural proteins specifically in CSF takes place. This study inquires into the physiological concentrations of NSE and S100B proteins in CSF, carried out on a sufficiently large group of 601 patients. The detected values can be used for determination of a normal reference range in CSF in a clinical laboratory diagnostics. PMID:26421286

  14. Prevalence of human Herpesviridae in cerebrospinal fluid of patients with multiple sclerosis and noninfectious neurological disease in the Netherlands.

    PubMed

    van Nierop, Gijsbert P; Hintzen, Rogier Q; Verjans, Georges M G M

    2014-08-01

    Prevalence of eight human herpesviruses (HHV1-8) was determined by real-time PCR in cell-rich cerebrospinal fluid (CSF) samples, obtained early after disease symptoms, of Dutch patients with multiple sclerosis (MS) and other noninfectious central nervous system diseases (NIND). Whereas HHV1-8 DNA was undetectable in CSF samples of MS patients, HHV6 DNA was detected in a plexus neuritis case and HHV7 DNA in an ependymoma and a Behçets' disease patient. However, intrathecal HHV infection was not detected. Data indicate that HHV1-8 are rarely detected in CSF of Dutch NIND patients and do not support the role of intrathecal HHV infection early after onset of disease symptoms in MS. PMID:24671719

  15. Antibodies to DNA repair proteins in headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL) patients.

    PubMed

    Erda?, Ece; Çelebisoy, Ne?e; Yüceyar, Ay?e Nur; Kürtüncü, Murat; Vural, Burçak; Tüzün, Erdem

    2015-06-01

    Autoimmune mechanisms have been implicated in the pathogenesis of headache and neurological deficits with cerebrospinal fluid lymphocytosis (HaNDL). Pooled sera of five HaNDL patients and 30 controls (10 multiple sclerosis patients, 10 migraine patients, 10 healthy controls) were screened by protein macroarray. All sera were also individually subjected to immunoprecipitation with neuroblastoma cells and the bound antigens were identified by mass spectrometry. Antibodies to three DNA repair proteins (mitogen-activated protein kinase-4, DNA-dependent protein kinase catalytic subunit, DNA excision repair protein ERCC-6) were identified by both macroarray and immunoprecipitation methods in 3/5 HaNDL sera, but in none of the controls. The presence of DNA repair protein antibodies indicates DNA damage and provides further support for the inflammatory etiology of HaNDL. PMID:25070837

  16. Toxoplasma-SPECIFIC IgG SUBCLASS ANTIBODY RESPONSE IN CEREBROSPINAL FLUID SAMPLES FROM PATIENTS WITH CEREBRAL TOXOPLASMOSIS

    PubMed Central

    NASCIMENTO, Fernanda S.; SUZUKI, Lisandra A.; BRANCO, Nilson; FRANCO, Regina M.B.; ANDRADE, Paula D.; COSTA, Sandra C.B.; PEDRO, Marcelo N.; ROSSI, Cláudio L.

    2015-01-01

    SUMMARY Cerebral toxoplasmosis can be highly debilitating and occasionally fatal in persons with immune system deficiencies. In this study, we evaluated the Toxoplasma gondii-specific IgG subclass antibody response in 19 cerebrospinal fluid (CSF) samples from patients with cerebral toxoplasmosis who had a positive IgG anti-T. gondiiELISA standardized with a cyst antigen preparation. There were no significant differences between the rates of positivity and the antibody concentrations (arithmetic means of the ELISA absorbances, MEA) for IgG1 and IgG2, but the rates of positivity and MEA values for these two IgG subclasses were significantly higher than those for IgG3 and IgG4. The marked IgG2 response in CSF from patients with cerebral toxoplasmosis merits further investigation. PMID:26603234

  17. Transcytosis in the blood–cerebrospinal fluid barrier of the mouse brain with an engineered receptor/ligand system

    PubMed Central

    Méndez-Gómez, Héctor R; Galera-Prat, Albert; Meyers, Craig; Chen, Weijun; Singh, Jasbir; Carrión-Vázquez, Mariano; Muzyczka, Nicholas

    2015-01-01

    Crossing the blood–brain and the blood–cerebrospinal fluid barriers (BCSFB) is one of the fundamental challenges in the development of new therapeutic molecules for brain disorders because these barriers prevent entry of most drugs from the blood into the brain. However, some large molecules, like the protein transferrin, cross these barriers using a specific receptor that transports them into the brain. Based on this mechanism, we engineered a receptor/ligand system to overcome the brain barriers by combining the human transferrin receptor with the cohesin domain from Clostridium thermocellum, and we tested the hybrid receptor in the choroid plexus of the mouse brain with a dockerin ligand. By expressing our receptor in choroidal ependymocytes, which are part of the BCSFB, we found that our systemically administrated ligand was able to bind to the receptor and accumulate in ependymocytes, where some of the ligand was transported from the blood side to the brain side. PMID:26491705

  18. Diagnosis of neuroschistosomiasis by antibody specificity index and semi-quantitative real-time PCR from cerebrospinal fluid and serum.

    PubMed

    Härter, Georg; Frickmann, Hagen; Zenk, Sebastian; Wichmann, Dominic; Ammann, Bettina; Kern, Peter; Fleischer, Bernhard; Tannich, Egbert; Poppert, Sven

    2014-02-01

    We describe the case of a 16-year-old German male expatriate from Ghana who presented with obstipation, dysuria, dysaesthesia of the gluteal region and the lower limbs, bilateral plantar hypaesthesia and paraesthesia without pareses. A serum-cerebrospinal fluid (CSF) Schistosoma spp. specific antibody specificity index of 3.1 was considered highly suggestive of intrathecal synthesis of anti-Schistosoma spp. specific antibodies, although standardization of this procedure has not previously been described. Diagnosis was confirmed by detection of Schistosoma DNA in CSF by semi-quantitative real-time PCR at 100-fold concentration compared with serum. Accordingly the two diagnostic procedures, which have not previously been applied for routine diagnosis, appear to be useful for the diagnosis of neuroschistosomiasis. Clinical symptoms resolved following anthelmintic and anti-inflammatory therapy. PMID:24227876

  19. Benefit of cerebrospinal fluid spectrophotometry in the assessment of CT scan negative suspected subarachnoid haemorrhage: a diagnostic accuracy study.

    PubMed

    Hann, Angus; Chu, Kevin; Greenslade, Jaimi; Williams, Julian; Brown, Anthony

    2015-01-01

    This study aimed to determine if performing cerebrospinal fluid spectrophotometry in addition to visual inspection detects more ruptured cerebral aneurysms than performing cerebrospinal fluid visual inspection alone in patients with a normal head CT scan but suspected of suffering an aneurysmal subarachnoid haemorrhage (SAH). We performed a single-centre retrospective study of patients presenting to the emergency department of a tertiary hospital who underwent both head CT scan and lumbar puncture to exclude SAH. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of an approach utilising both spectrophotometry and visual inspection (combined approach) was compared to visual inspection alone. A total of 409 patients (mean age 37.8 years, 56.2% female) were recruited and six (1.5%) had a cerebral aneurysm on angiography. The sensitivity of visual inspection was 50% (95% confidence interval [CI]: 12.4-82.6%), specificity was 99% (95% CI: 97.5-99.7%), PPV was 42.9% (95% CI: 10.4-81.3%) and NPV was 99.2% (95% CI: 97.8-99.8%). The combined approach had a sensitivity of 100% (95% CI: 54.1-100%), specificity of 79.7% (95% CI: 75.4-83.5%), PPV of 6.8% (95% CI: 2.6-14.3%) and a NPV of 100% (95% CI: 98.8-100%). The sensitivity of the combined approach was not significantly different to that of visual inspection alone (p=0.25). Visual inspection had a significantly higher specificity than the combined approach (p<0.01). The combined approach detected more cases of aneurysmal SAH than visual inspection alone, however the difference in sensitivity was not statistically significant. Visual xanthochromia should prompt angiography because of a superior specificity and PPV. Due to its reduced sensitivity, caution should be applied when using only visual inspection of the supernatant. PMID:25439758

  20. The Incidence and Management of Dural Tears and Cerebrospinal Fluid Leakage during Corrective Osteotomy for Ankylosing Spondylitis with Kyphotic Deformity

    PubMed Central

    Jo, Dae-Jean; Kim, Ki-Tack; Lee, Sang-Hun; Cho, Myung-Guk

    2015-01-01

    Objective To present the incidence and management of dural tears and cerebrospinal fluid leakage during corrective osteotomy [Pedicle Subtraction Osteotomy (PSO) or Smith-Petersen Osteotomy (SPO)] for ankylosing spondylitis with kyphotic deformity. Methods A retrospective study was performed for ankylosing spondylitis patients with fixed sagittal imbalance, who had undergone corrective osteotomy (PSO or SPO) at lumbar level. 87 patients were included in this study. 55 patients underwent PSO, 32 patients underwent SPO. The mean age of the patients at the time of surgery was 41.7 years (21-70 years). Of the 87 patients, 15 patients had intraoperative dural tears. Results The overall incidence of dural tears was 17.2%. The incidence of dural tears during PSO was 20.0%, SPO was 12.5%. There was significant difference in the incidence of dural tears based on surgical procedures (PSO vs. SPO) (p<0.05). The dural tears ranged in size from 12 to 221 mm2. A nine of 15 patients had the relatively small dural tears, underwent direct repair via watertight closure. The remaining 6 patients had the large dural tears, consequently direct repair was impossible. The large dural tears were repaired with an on-lay graft of muscle, fascia or fat harvested from the adjacent operation site. All patients had a successful repair with no patient requiring reoperation for the cerebrospinal fluid leak. Conclusion The overall incidence of dural tears during PSO or SPO for ankylosing spondylitis with kyphotic deformity was 17.2%. The risk factor of dural tears was complexity of surgery. All dural tears were repaired primarily using direct suture, muscle, fascia or fat graft. PMID:26279815

  1. [Pneumococcal meningitis in a pregnant woman].

    PubMed

    Scharek, Petra; Jekkel, Csilla; Budai, József; Szilasi, Zsuzsanna; Helferich, Frigyes; Arva, Ilona; Váradi, András; Létay, Erzsébet; Katona, Katalin; Rókusz, László

    2014-01-30

    Bacterial meningitis is a life-threatening disease. The incidence of meningitis is about 2.6-6 cases per 100.000 adults per year in developed countries. The most common causative microorganisms are Sreptococcus pneumoniae and Neisseria meningitidis. A 33-year-old multigravida, at 24 week of gestation was admitted to the hospital because of ear pain, haedache, fever and confusion. Lumbal puncture was performed and cerebrospinal fluid analysis showed signs of bacterial meningitis. Latex agglutination test was positive for S. pneumoniae, Gram-positive diplococci have seen under microscope and later cultivation verified S. pneumoniae as the causative agent. After ceftriaxon, dexamethasone administration and treatment in intensive care unit, left side mastoidectomy was performed since cranial computed tomography showed acut exacerbation of chronic mastoiditis on the left side. After extubation, mobilisation and 14 days antibiotic treatment the patient, who had residual hearing loss on the left side, was discharged from the hospital. During the treatment the foetal parameters were normal. The patient at 39 week of gestation gave birth to a healthy infant. Forty-eight case reports have been published in this topic around the world until April, 2012. The most common causative agents were S. pneumoniae and Listeria monocytogenes. Because of the little amount of data, it is hard to appreciate the actual incidence and prognosis of this life-threatening illness both for mother and infant. As far as we know this is the first published case report of meningitis during pregnancy in Hungary. By this article we would like to draw attention to the importance of teamwork, of prevention of brain abscess formation and of the removal of the infection's focus. PMID:24654448

  2. Treating Meningitis

    MedlinePLUS

    ... David C. Spencer, MD Steven Karceski, MD Treating meningitis Steven Karceski, MD WHAT DID THE AUTHORS STUDY? ... study, “ Dexamethasone and long-term survival in bacterial meningitis, ” Dr. Fritz and his colleagues carefully evaluated 2 ...

  3. Two cases of medically-refractory spontaneous orthostatic headaches with normal cerebrospinal fluid pressures responding to epidural blood patching: Intracranial hypotension versus hypovolemia and the need for clinical awareness

    PubMed Central

    Hassan, Kaukab M.; Prakash, Sudeep; Majumdar, S. S.; Banerji, Anup

    2013-01-01

    The diagnosis of spontaneous intracranial hypotension or cerebrospinal fluid (CSF) hypovolemia syndrome requires a high index of suspicion and meticulous history taking, demonstration of low CSF pressure and/or neuroimaging features. A 31-year-old male, presented with subacute onset moderate occipital and sub-occipital headaches precipitated by upright posture and relieved on recumbency and neck pain for 2 years. There was no trauma, cranial/spinal surgery. Clinical examination was normal and CSF opening pressure and laboratory study were normal. Magnetic resonance imaging (MRI) brain showed thin subdural hygroma. Another patient, 41-year-old male presented with 1 month of subacute onset severe bifrontal throbbing orthostatic headaches (OHs). CSF opening pressure was normal. Contrast MRI brain showed the presence of bilateral subdural hygromas, diffuse meningeal enhancement, venous distension, sagging of the brain, and tonsillar herniation. We report two cases of “spontaneous OHs” with normal CSF pressures who were successfully treated with epidural blood patching after poor response to conservative management. PMID:24339614

  4. Platelet-activating factor augments meningeal inflammation elicited by Haemophilus influenzae lipooligosaccharide in an animal model of meningitis.

    PubMed Central

    Townsend, G C; Scheld, W M

    1994-01-01

    Research into the pathophysiology of bacterial meningitis has suggested a role for various endogenous inflammatory mediators, such as platelet-activating factor (PAF). In the present study, rats were inoculated intracisternally with various doses of PAF, with Haemophilus influenzae lipooligosaccharide (LOS) in high doses (20 ng) alone, and with a low dose of LOS (200 pg) with or without low doses of PAF (25 ng to 2.5 micrograms). Values for cerebrospinal fluid leukocytosis and percent blood-brain barrier permeability to systemically administered 125I-labeled albumin observed after inoculation of low-dose LOS with PAF were greater (P < 0.05) than those observed after inoculation of low-dose LOS alone and not statistically different from those observed after inoculation of high-dose LOS. PAF alone elicited an inflammatory response only at high doses (25 micrograms). These results support the hypothesis that low cerebrospinal fluid PAF concentrations, such as those observed in children with bacterial meningitis, may augment the inflammatory response to the presence of bacteria in the subarachnoid space. PMID:8063388

  5. Extracellular chaperones modulate the effects of Alzheimer’s patient cerebrospinal fluid on A?1-42 toxicity and uptake

    PubMed Central

    Wilson, Mark R.

    2009-01-01

    Alzheimer’s disease is characterised by the inappropriate death of brain cells and accumulation of the A? peptide in the brain. Thus, it is possible that there are fundamental differences between Alzheimer’s disease patients and healthy individuals in their abilities to clear A? from brain fluid and to protect neurons from A? toxicity. In the present study, we examined (1) the cytotoxicity of Alzheimer’s disease cerebrospinal fluid (CSF) compared to control CSF, (2) the ability of Alzheimer’s disease and control CSF to protect cells from A? toxicity and to promote cell-mediated clearance of A? and lastly (3) the effects of extracellular chaperones, normally found in CSF, on these processes. We show that the Alzheimer’s disease CSF samples tested were more toxic to cultured neuroblastoma cells than normal CSF. In addition, the Alzheimer’s disease CSF samples tested were less able to protect cells from A?-induced toxicity and less efficient at promoting macrophage-like cell uptake when compared to normal CSF. The addition of physiologically relevant concentrations of the extracellular chaperones, clusterin, haptoglobin and ?2-macroglobulin into CSF protected neuroblastoma cells from ??1-42 toxicity and promoted ??1-42 uptake in macrophage-like cells. These results suggest that extracellular chaperones are an important element of a system of extracellular protein folding quality control that protects against A? toxicity and accumulation. PMID:19472074

  6. Age-Dependent Changes in the Cerebrospinal Fluid Proteome by Slow Off-Rate Modified Aptamer Array

    PubMed Central

    Baird, Geoffrey S.; Nelson, Sally K.; Keeney, Tracy R.; Stewart, Alex; Williams, Stephen; Kraemer, Stephan; Peskind, Elaine R.; Montine, Thomas J.

    2012-01-01

    An important precondition for the successful development of diagnostic assays of cerebrospinal fluid (CSF) biomarkers of age-related neurodegenerative diseases is an understanding of the dynamic nature of the CSF proteome during the normal aging process. In this study, a novel proteomic technology was used to quantify hundreds of proteins simultaneously in the CSF from 90 cognitively normal adults 21 to 85 years of age. SomaLogic's highly multiplexed proteomic platform can measure more than 800 proteins simultaneously from small volumes of biological fluids using novel slow off-rate modified aptamer (SOMAmer) protein affinity reagents with sensitivity, specificity, and dynamic ranges that meet or exceed those of enzyme-linked immunosorbent assays. In the first application of this technology to CSF, we detected 248 proteins that possessed signals greater than twofold over background. Several novel correlations between detected protein concentrations and age were discovered that indicate that both inflammation and response to injury in the central nervous system may increase with age. Applying this powerful proteomic approach to CSF provides potential new insight into the aging of the human central nervous system that may have utility in discovering new disease-related changes in the CSF proteome. PMID:22122984

  7. Gray-white matter and cerebrospinal fluid volume differences in children with Specific Language Impairment and/or Reading Disability.

    PubMed

    Girbau-Massana, Dolors; Garcia-Marti, Gracian; Marti-Bonmati, Luis; Schwartz, Richard G

    2014-04-01

    We studied gray-white matter and cerebrospinal fluid (CSF) alterations that may be critical for language, through an optimized voxel-based morphometry evaluation in children with Specific Language Impairment (SLI), compared to Typical Language Development (TLD). Ten children with SLI (8;5-10;9) and 14 children with TLD (8;2-11;8) participated. They received a comprehensive language and reading test battery. We also analyzed a subgroup of six children with SLI+RD (Reading Disability). Brain images from 3-Tesla MRIs were analyzed with intelligence, age, gender, and total intracranial volume as covariates. Children with SLI or SLI+RD exhibited a significant lower overall gray matter volume than children with TLD. Particularly, children with SLI showed a significantly lower volume of gray matter compared to children with TLD in the right postcentral parietal gyrus (BA4), and left and right medial occipital gyri (BA19). The group with SLI also exhibited a significantly greater volume of gray matter in the right superior occipital gyrus (BA19), which may reflect a brain reorganization to compensate for their lower volumes at medial occipital gyri. Children with SLI+RD, compared to children with TLD, showed a significantly lower volume of: (a) gray matter in the right postcentral parietal gyrus; and (b) white matter in the right inferior longitudinal fasciculus (RILF), which interconnects the temporal and occipital lobes. Children with TLD exhibited a significantly lower CSF volume than children with SLI and children with SLI+RD respectively, who had somewhat smaller volumes of gray matter allowing for more CSF volume. The significant lower gray matter volume at the right postcentral parietal gyrus and greater cerebrospinal fluid volume may prove to be unique markers for SLI. We discuss the association of poor knowledge/visual representations and language input to brain development. Our comorbid study showed that a significant lower volume of white matter in the right inferior longitudinal fasciculus may be unique to children with SLI and Reading Disability. It was significantly associated to reading comprehension of sentences and receptive language composite z-score, especially receptive vocabulary and oral comprehension of stories. PMID:24418156

  8. Mobile and cordless telephones, serum transthyretin and the blood-cerebrospinal fluid barrier: a cross-sectional study

    PubMed Central

    2009-01-01

    Background Whether low-intensity radiofrequency radiation damages the blood-brain barrier has long been debated, but little or no consideration has been given to the blood-cerebrospinal fluid barrier. In this cross-sectional study we tested whether long-term and/or short-term use of wireless telephones was associated with changes in the serum transthyretin level, indicating altered transthyretin concentration in the cerebrospinal fluid, possibly reflecting an effect of radiation. Methods One thousand subjects, 500 of each sex aged 18–65 years, were randomly recruited using the population registry. Data on wireless telephone use were assessed by a postal questionnaire and blood samples were analyzed for serum transthyretin concentrations determined by standard immunonephelometric techniques on a BN Prospec® instrument. Results The response rate was 31.4%. Logistic regression of dichotomized TTR serum levels with a cut-point of 0.31 g/l on wireless telephone use yielded increased odds ratios that were statistically not significant. Linear regression of time since first use overall and on the day that blood was withdrawn gave different results for males and females: for men significantly higher serum concentrations of TTR were seen the longer an analogue telephone or a mobile and cordless desktop telephone combined had been used, and in contrast, significantly lower serum levels were seen the longer an UMTS telephone had been used. Adjustment for fractions of use of the different telephone types did not modify the effect for cumulative use or years since first use for mobile telephone and DECT, combined. For women, linear regression gave a significant association for short-term use of mobile and cordless telephones combined, indicating that the sooner blood was withdrawn after the most recent telephone call, the higher the expected transthyretin concentration. Conclusion In this hypothesis-generating descriptive study time since first use of mobile telephones and DECT combined was significantly associated with higher TTR levels regardless of how much each telephone type had been used. Regarding short-term use, significantly higher TTR concentrations were seen in women the sooner blood was withdrawn after the most recent telephone call on that day. PMID:19383125

  9. HSV-1 as a novel therapy for breast cancer meningeal metastases.

    PubMed

    Kuruppu, D; Tanabe, K K

    2015-10-01

    Meningeal metastasis is a fatal complication of breast cancer that affects 5-8% of patients. When cancer cells seed in the meninges, their subsequent growth results in severe neurological complications involving the cranial nerves, cerebrum and spinal cord, limiting life expectancy to less than 4 months. The incidences of meningeal metastases increase with prolonged lifespan resulting from treatment advances for primary breast cancer and their metastases. Currently, there is no cure. Aggressive multimodal therapies such as radiation and chemotherapy (intra-cerebrospinal fluid (CSF) and systemic) are ineffective. Therapeutic agents are often quickly cleared from the CSF, while higher doses that can achieve a therapeutic response are highly toxic. The secure guarding of the subarachnoid space by the blood-brain barrier on one side and the blood-CSF barrier on the other prevents chemotherapy from reaching cancer cells in the meninges. These challenges with treating meningeal metastases highlight the urgent need for a new therapeutic modality. An ideal treatment would be an agent that avoids rapid clearance, remains within the CSF, reaches the meninges and selectively destroys tumor cells. Replication conditional oncolytic herpes simplex virus type 1 (HSV-1) may be effective in this regard. Viral oncolysis, the destruction of cancer cells by replicating virus, is under clinical investigation for cancers that are unresponsive to current therapies. It is based on the model of multiple cycles of lytic virus replication in cancer cells that amplify the injected dose. The therapeutic potential of oncolytic HSV-1 for breast cancer meningeal metastases is discussed here. HSV-1 could be a potential novel treatment for meningeal metastases that can be translated to the clinic. PMID:26384139

  10. Tuberculous meningitis with dementia as the presenting symptom after intramedullary spinal cord tumor resection

    PubMed Central

    Kobayashi, Kazuyoshi; Imagama, Shiro; Ito, Zenya; Ando, Kei; Yagi, Hideki; Shinjo, Ryuichi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    ABSTRACT Early-stage TB meningitis has no specific symptoms in patients, potentially leading to delayed diagnosis and consequently worsening prognosis. The authors present the fatal case with a delayed diagnosis of tuberculous (TB) meningitis with dementia as the presenting symptom after intramedullary spinal cord tumor resection. The medical records, operative reports, and radiographical imaging studies of a single patient were retrospectively reviewed. A 77-year-old man who underwent thoracic intramedullary hemangioblastoma resection for 2 times. The postoperative course was uneventful, but 1.5 months after surgery, the patient suffered from dementia with memory loss and diminished motivation and speech in the absence of a fever. No abnormalities were detected on blood test, brain computed tomography and cerebrospinal fluid (CSF) analysis. A sputum sample was negative for Mycobacterium tuberculosis in the QuantiFERON®-TB Gold (QFT-G) In-Tube Test and the tuberculin skin test was also negative. The patient was diagnosed with senile dementia by a psychiatrist. However, the patient’s symptoms progressively worsened. Despite the absence of TB meningitis findings, we suspected TB meningitis from the patient’s history, and administered a four-drug regimen. However the patient died 29 days after admission, subsequently M. tuberculosis was detected in the CSF sample. This case is a rare case of TB meningitis initially mistaken for dementia after intramedullary spinal cord tumor resection. Symptoms of dementia after intramedullary spinal cord tumor resection should first be suspected as one of TB meningitis, even if the tests for meningitis are negative. We propose that anti-tuberculosis therapy should be immediately initiated in cases of suspected TB meningitis prior to positive identification on culture.

  11. Abeta peptide 1-42, Tau protein and S-100B protein level in cerebrospinal fluid of three patients with primary progressive aphasia.

    PubMed

    Maeck, Lienhard; Meller, Johannes; Otto, Markus; Stiens, Gerthild; Wiltfang, Jens; Stoppe, Gabriela

    2002-11-15

    Primary progressive aphasia (PPA) is a clinical syndrome characterized by a slowly progressive aphasia in the absence of accompanying signs of generalized dementia. While non-fluent PPA tends to progress frontally and is usually linked to frontotemporal degeneration, fluent PPA might be associated with both, frontotemporal degeneration or Alzheimer's disease. Although recent reports suggest that PPA belongs neuropathologically to the group of tauopathias, cerebrospinal fluid analysis has not been established as a means of diagnosis in PPA so far. In this paper we investigated Abeta peptide(1-42) (Abeta(1-42)), Tau protein and S-100B protein level in the cerebrospinal fluid of three patients with PPA. In all patients Tau protein and S-100B level were slightly elevated, however, Abeta(1-42) was found to be in normal range. Thus, our first results point to PPA being neurochemically linked to frontotemporal degeneration. PMID:12401554

  12. Effects of Anesthetic Isoflurane and Desflurane on Human Cerebrospinal Fluid A? and ? Level

    PubMed Central

    Zhang, Bin; Tian, Ming; Zheng, Hui; Zhen, Yu; Yue, Yun; Li, Tianzuo; Li, Shuren; Marcantonio, Edward R.; Xie, Zhongcong

    2014-01-01

    Background Accumulation of ?-amyloid protein (A?) and tau protein is the main feature of Alzheimer disease neuropathogenesis. Anesthetic isoflurane, but not desflurane, may increase A? levels in vitro and in animals. Therefore, we set out to determine the efects of isoflurane and desflurane on cerebrospinal fuid (CSF) levels of A? and tau in humans. Methods The participants were assigned into spinal anesthesia (N = 35), spinal plus desflurane anesthesia (N = 33), or spinal plus isoflurane anesthesia (N = 38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of A? (A?40 and A?42) and total tau in the CSF were determined. Results Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF A?40 levels (from 10.90 to 12.41 ng/ml) 24 h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P = 0.022. Desflurane, but not isoflurane, was associated with a decrease in A?42 levels 2 h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44 ng/ml), P = 0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. Conclusions These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF A? levels. PMID:23438677

  13. Preparation and application of a novel molecularly imprinted solid-phase microextraction monolith for selective enrichment of cholecystokinin neuropeptides in human cerebrospinal fluid.

    PubMed

    Ji, Xiang; Li, Dan; Li, Hua

    2015-08-01

    A novel molecularly imprinted polymer (MIP) monolith for highly selective extraction of cholecystokinin (CCK) neuropeptides was prepared in a micropipette tip. The MIPs were synthesized by epitope imprinting technique and the polymerization conditions were investigated and optimized. The synthesized MIPs were characterized by infrared spectroscopy, elemental analyzer and scanning electron microscope. A molecularly imprinted solid-phase microextraction (MI-?-SPE) method was developed for the extraction of CCK neuropeptides in aqueous solutions. The parameters affecting MI-?-SPE were optimized. The results indicated that this MIP monolith exhibited specific recognition capability and high enrichment efficiency for CCK neuropeptides. In addition, it showed excellent reusability. This MIP monolith was used for desalting and enrichment of CCK4, CCK5 and CCK8 from human cerebrospinal fluid prior to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, and the results show that this MIP monolith can be a useful tool for effective purification and highly selective enrichment of multiple homologous CCK neuropeptides in cerebrospinal fluid simultaneously. By employing MI-?-SPE combined with HPLC-ESI-MS/MS analysis, endogenous CCK4 in human cerebrospinal fluid was quantified. PMID:25616243

  14. Meningitis (For Parents)

    MedlinePLUS

    ... Kids Deal With Bullies Pregnant? What to Expect Meningitis KidsHealth > Parents > Infections > Lung & Respiratory Infections > Meningitis Print ... Spreads Prevention When to Call the Doctor About Meningitis Meningitis is an inflammation of the meninges, the ...

  15. Meningitis - staphylococcal

    MedlinePLUS

    Staphylococcal meningitis is caused by Staphylococcus bacteria. When it is caused by Staphylococcus aureus or Staphylococcus epidermidis bacteria, it usually develops as a complication of surgery or ...

  16. Validation of a quantitative cerebrospinal fluid alpha-synuclein assay in a European-wide interlaboratory study.

    PubMed

    Kruse, Niels; Persson, Staffan; Alcolea, Daniel; Bahl, Justyna M C; Baldeiras, Ines; Capello, Elisabetta; Chiasserini, Davide; Bocchio Chiavetto, Luisella; Emersic, Andreja; Engelborghs, Sebastiaan; Eren, Erden; Fladby, Tormod; Frisoni, Giovanni; García-Ayllón, María-Salud; Genc, Sermin; Gkatzima, Olymbia; Heegaard, Niels H H; Janeiro, André M; Ková?ech, Branislav; Kuiperij, H Bea; Leitão, Maria J; Lleó, Alberto; Martins, Madalena; Matos, Mafalda; Mollergard, Hanne M; Nobili, Flavio; Öhrfelt, Annika; Parnetti, Lucilla; de Oliveira, Catarina Resende; Rot, Uros; Sáez-Valero, Javier; Struyfs, Hanne; Tanassi, Julia T; Taylor, Peggy; Tsolaki, Magda; Vanmechelen, Eugeen; Verbeek, Marcel M; Zilka, Norbert; Blennow, Kaj; Zetterberg, Henrik; Mollenhauer, Brit

    2015-09-01

    Decreased levels of alpha-synuclein (aSyn) in cerebrospinal fluid (CSF) in Parkinson's disease and related synucleinopathies have been reported, however, not consistently in all cross-sectional studies. To test the performance of one recently released human-specific enzyme-linked immunosorbent assay (ELISA) for the quantification of aSyn in CSF, we carried out a round robin trial with 18 participating laboratories trained in CSF ELISA analyses within the BIOMARKAPD project in the EU Joint Program - Neurodegenerative Disease Research. CSF samples (homogeneous aliquots from pools) and ELISA kits (one lot) were provided centrally and data reported back to one laboratory for data analysis. Our study showed that although factors such as preanalytical sample handling and lot-to-lot variability were minimized by our study design, we identified high variation in absolute values of CSF aSyn even when the same samples and same lots of assays were applied. We further demonstrate that although absolute concentrations differ between laboratories the quantitative results are comparable. With further standardization this assay may become an attractive tool for comparing aSyn measurements in diverse settings. Recommendations for further validation experiments and improvement of the interlaboratory results obtained are given. PMID:26093515

  17. Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects.

    PubMed

    Carpenter, Linda L; Tyrka, Audrey R; McDougle, Christopher J; Malison, Robert T; Owens, Michael J; Nemeroff, Charles B; Price, Lawrence H

    2004-04-01

    Previous studies have reported elevated concentrations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) in patients with major depression. Elevations of CSF CRF have also been reported in adult laboratory animals exposed to the stress of brief maternal deprivation or maternal neglect in the neonatal or preweaning period. The present study was designed to determine whether major depression and a history of perceived early adversity in childhood are independently associated with elevated CSF CRF concentrations in adults. In this case-control study, 27 medication-free adults with major depression and 25 matched controls underwent standardized lumbar puncture for collection of a single CSF sample at 1200. Subjects provided data about significant adverse early-life experiences and rated their global perceived level of stress during pre-school and preteen years on a six-point Likert scale. The mean difference in CSF CRF between depressed patients and controls did not reach statistical significance. In a regression model, perceived early-life stress was a significant predictor of CSF CRF, but depression was not. Perinatal adversity and perceived adversity in the preteen adversity years (ages 6-13 years) were both independently associated with decreasing CSF CRF concentrations. The relationship observed between perceived early-life stress and adult CSF CRF concentrations in this study closely parallels recent preclinical findings. More work is needed to elucidate the critical nature and timing of early events that may be associated with enduring neuroendocrine changes in humans. PMID:14702025

  18. Preanalytical Confounding Factors in the Analysis of Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: The Issue of Diurnal Variation

    PubMed Central

    Cicognola, Claudia; Chiasserini, Davide; Parnetti, Lucilla

    2015-01-01

    Given the growing use of cerebrospinal fluid (CSF) beta-amyloid (A?) and tau as biomarkers for early diagnosis of Alzheimer’s disease (AD), it is essential that the diagnostic procedures are standardized and the results comparable across different laboratories. Preanalytical factors are reported to be the cause of at least 50% of the total variability. Among them, diurnal variability is a key issue and may have an impact on the comparability of the values obtained. The available studies on this issue are not conclusive so far. Fluctuations of CSF biomarkers in young healthy volunteers have been previously reported, while subsequent studies have not confirmed those observations in older subjects, the ones most likely to receive this test. The observed differences in circadian rhythms need to be further assessed not only in classical CSF biomarkers but also in novel forthcoming biomarkers. In this review, the existing data on the issue of diurnal variations of CSF classical biomarkers for AD will be analyzed, also evaluating the available data on new possible biomarkers. PMID:26175714

  19. Polymorphisms in genes implicated in dopamine, serotonin and noradrenalin metabolism suggest association with cerebrospinal fluid monoamine metabolite concentrations in psychosis

    PubMed Central

    2014-01-01

    Background Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) are the major monoamine metabolites in the central nervous system (CNS). Their cerebrospinal fluid (CSF) concentrations, reflecting the monoamine turnover rates in CNS, are partially under genetic influence and have been associated with schizophrenia. We have hypothesized that CSF monoamine metabolite concentrations represent intermediate steps between single nucleotide polymorphisms (SNPs) in genes implicated in monoaminergic pathways and psychosis. Methods We have searched for association between 119 SNPs in genes implicated in monoaminergic pathways [tryptophan hydroxylase 1 (TPH1), TPH2, tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), dopamine beta-hydroxylase (DBH), catechol-O-methyltransferase (COMT), monoamine oxidase A (MAOA) and MAOB] and monoamine metabolite concentrations in CSF in 74 patients with psychotic disorder. Results There were 42 nominally significant associations between SNPs and CSF monoamine metabolite concentrations, which exceeded the expected number (20) of nominal associations given the total number of tests performed. The strongest association (p =?0.0004) was found between MAOB rs5905512, a SNP previously reported to be associated with schizophrenia in men, and MHPG concentrations in men with psychotic disorder. Further analyses in 111 healthy individuals revealed that 41 of the 42 nominal associations were restricted to patients with psychosis and were absent in healthy controls. Conclusions The present study suggests that altered monoamine turnover rates in CNS reflect intermediate steps in the associations between SNPs and psychosis. PMID:25073638

  20. Cerebrospinal fluid protein and glucose examinations and tuberculosis:?Will laboratory safety regulations force a change of practice?

    PubMed Central

    Tormey, William P.; O’Hagan, Christopher

    2015-01-01

    Cerebrospinal fluid (CSF) protein and glucose examinations are usually performed in chemical pathology departments on autoanalysers. Tuberculosis (TB) is a group 3 biological agent under Directive 2000/54/EC of the European Parliament but in the biochemistry laboratory, no extra precautions are taken in its analysis in possible TB cases. The issue of laboratory practice and safety in the biochemical analyses of CSF specimens, when tuberculosis infection is in question is addressed in the context of ambiguity in the implementation of current national and international health and safety regulations. Additional protective measures for laboratory staff during the analysis of CSF TB samples should force a change in current laboratory practice and become a regulatory issue under ISO 15189. Annual Mantoux skin test or an interferon-? release assay for TB should be mandatory for relevant staff. This manuscript addresses the issue of biochemistry laboratory practice and safety in the biochemical analyses of CSF specimens when tuberculosis infection is in question in the context of the ambiguity of statutory health and safety regulations. PMID:26526598

  1. Correlations between Alzheimer's Disease Cerebrospinal Fluid Biomarkers and Cerebral Glucose Metabolism after 12 Months of Phenserine Treatment.

    PubMed

    Nordberg, Agneta; Kadir, Ahmadul; Andreasen, Niels; Almkvist, Ove; Wall, Anders; Långström, Bengt; Zetterberg, Henrik

    2015-08-01

    New therapeutic strategies in Alzheimer's disease (AD) are focused on targeting amyloid-? (A?) to modify the underlying cause of the disease rather than just the symptoms. The aim of this study was to investigate the long-term effects of treatment with the anti-A? compound phenserine on (i) cerebrospinal fluid (CSF) biomarkers for A? and tau pathology and (ii) brain metabolism as assessed by the regional cerebral metabolic rate for glucose (rCMRglc), using positron emission tomography. Twenty patients with mild AD were included in the study and after 12 months treatment with phenserine, CSF A? 40 and ?- and ?-secretase-cleaved soluble amyloid-? protein precursor (sA?PP) levels had significantly increased and rCMRglc had stabilized. Levels of CSF A? 40 and sA?PP correlated positively with rCMRglc and cognition while CSF A? 42 levels, the A? 42/40 ratio, P-tau, and T-tau correlated negatively with rCMRglc and cognition. In summary, long-term phenserine treatment resulted in increased levels of CSF A? 40, sA?PP?, and sA?PP?, which positively correlated with improvements in rCMRglc and cognition. The study illustrates the value of using biomarkers in the CSF and brain for evaluation of drug effects. PMID:26401704

  2. Central nervous system multiple myeloma--potential roles for intrathecal therapy and measurement of cerebrospinal fluid light chains.

    PubMed

    Lee, Denise; Kalff, Anna; Low, Michael; Gangatharan, Shane; Ho, Prahlad; Bajel, Ashish; Ritchie, David; Grigg, Andrew; Spencer, Andrew

    2013-08-01

    Central nervous system (CNS) multiple myeloma (MM) is exceedingly rare and portends a dismal prognosis. While immunomodulators have contributed to the improvement in survival in MM, they appear to have limited activity against CNS MM and, paradoxically, may contribute to the evolution of resistant MM clones capable of surviving within the CNS. We undertook a retrospective analysis to characterize the features of CNS MM and outcome in 17 patients from four institutions identified between 2000 and 2011. The median age was 58 years. Patients had received a median of three prior therapies and all had been exposed to at least one of the so-called novel anti-MM agents before the diagnosis of CNS MM. The median time to CNS disease from initial diagnosis was 36 months. Cerebrospinal fluid (CSF) light chain measurements produced discrepant results to serum light chain measurements in some patients. Treatments included systemic pharmacotherapy, intrathecal (IT) chemotherapy and/or radiotherapy (RT). The median overall survival (OS) from diagnosis of CNS MM was only 4 months. OS was significantly better in patients who received IT chemotherapy (20 months vs. 2 months, respectively; P < 0.02). We conclude that the systematic evaluation of IT therapy and diagnostic utility of CSF light chain measurements in CNS MM are warranted. PMID:23718539

  3. Cerebrospinal fluid biochemical studies in patients with Parkinson's disease: toward a potential search for biomarkers for this disease

    PubMed Central

    Jiménez-Jiménez, Félix J.; Alonso-Navarro, Hortensia; García-Martín, Elena; Agúndez, José A. G.

    2014-01-01

    The blood-brain barrier supplies brain tissues with nutrients and filters certain compounds from the brain back to the bloodstream. In several neurodegenerative diseases, including Parkinson's disease (PD), there are disruptions of the blood-brain barrier. Cerebrospinal fluid (CSF) has been widely investigated in PD and in other parkinsonian syndromes with the aim of establishing useful biomarkers for an accurate differential diagnosis among these syndromes. This review article summarizes the studies reported on CSF levels of many potential biomarkers of PD. The most consistent findings are: (a) the possible role of CSF urate on the progression of the disease; (b) the possible relations of CSF total tau and phosphotau protein with the progression of PD and with the preservation of cognitive function in PD patients; (c) the possible value of CSF beta-amyloid 1-42 as a useful marker of further cognitive decline in PD patients, and (d) the potential usefulness of CSF neurofilament (NFL) protein levels in the differential diagnosis between PD and other parkinsonian syndromes. Future multicentric, longitudinal, prospective studies with long-term follow-up and neuropathological confirmation would be useful in establishing appropriate biomarkers for PD. PMID:25426023

  4. Validation of a commercially available enzyme-linked immunoabsorbent assay for the quantification of human ?-Synuclein in cerebrospinal fluid.

    PubMed

    Kruse, Niels; Mollenhauer, Brit

    2015-11-01

    The quantification of ?-Synuclein in cerebrospinal fluid (CSF) as a biomarker has gained tremendous interest in the last years. Several commercially available immunoassays are emerging. We here describe the full validation of one commercially available ELISA assay for the quantification of ?-Synuclein in human CSF (Covance alpha-Synuclein ELISA kit). The study was conducted within the BIOMARKAPD project in the European initiative Joint Program for Neurodegenerative Diseases (JPND). We investigated the effect of several pre-analytical and analytical confounders: i.e. (1) need for centrifugation of freshly drawn CSF, (2) sample stability, (3) delay of freezing, (4) volume of storage aliquots, (5) freeze/thaw cycles, (6) thawing conditions, (7) dilution linearity, (8) parallelism, (9) spike recovery, and (10) precision. None of these confounders influenced the levels of ?-Synuclein in CSF significantly. We found a very high intra-assay precision. The inter-assay precision was lower than expected due to different performances of kit lots used. Overall the validated immunoassay is useful for the quantification of ?-Synuclein in human CSF. PMID:26271436

  5. Isobaric Quantification of Cerebrospinal Fluid Amyloid-? Peptides in Alzheimer's Disease: C-Terminal Truncation Relates to Early Measures of Neurodegeneration.

    PubMed

    Rogeberg, Magnus; Almdahl, Ina Selseth; Wettergreen, Marianne; Nilsson, Lars N G; Fladby, Tormod

    2015-11-01

    The amyloid beta (A?) peptide is the main constituent of the plaques characteristic of Alzheimer's disease (AD). Measurement of A?1-42 in cerebrospinal fluid (CSF) is a valuable marker in AD research, where low levels indicate AD. Although the use of immunoassays measuring A?1-38 and A?1-40 in addition to A?1-42 has increased, quantitative assays of other A? peptides remain rarely explored. We recently discovered novel A? peptides in CSF using antibodies recognizing the A? mid-domain region. Here we have developed a method using both A? N-terminal and mid-domain antibodies for immunoprecipitation in combination with isobaric labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for relative quantification of endogenous A? peptides in CSF. The developed method was used in a pilot study to produce A? peptide profiles from 38 CSF samples. Statistical comparison between CSF samples from 19 AD patients and 19 cognitively healthy controls revealed no significant differences at group level. A significant correlation was found between several larger C-terminally truncated A? peptides and protein biomarkers for neuronal damage, particularly prominent in the control group. Comparison of the isobaric quantification with immunoassays measuring A?1-38 or A?1-40 showed good correlation (r(2) = 0.84 and 0.85, respectively) between the two analysis methods. The developed method could be used to assess disease-modifying therapies directed at A? production or degradation. PMID:26452689

  6. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.

    PubMed

    De Mattos-Arruda, Leticia; Mayor, Regina; Ng, Charlotte K Y; Weigelt, Britta; Martínez-Ricarte, Francisco; Torrejon, Davis; Oliveira, Mafalda; Arias, Alexandra; Raventos, Carolina; Tang, Jiabin; Guerini-Rocco, Elena; Martínez-Sáez, Elena; Lois, Sergio; Marín, Oscar; de la Cruz, Xavier; Piscuoglio, Salvatore; Towers, Russel; Vivancos, Ana; Peg, Vicente; Cajal, Santiago Ramon Y; Carles, Joan; Rodon, Jordi; González-Cao, María; Tabernero, Josep; Felip, Enriqueta; Sahuquillo, Joan; Berger, Michael F; Cortes, Javier; Reis-Filho, Jorge S; Seoane, Joan

    2015-01-01

    Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis. PMID:26554728

  7. Insulin increases central apolipoprotein E levels as revealed by an improved technique for collection of cerebrospinal fluid from rats

    PubMed Central

    Liu, Min; Shen, Ling; Begg, Denovan P.; D’alessio, David A.; Woods, Stephen C.

    2012-01-01

    Cerebrospinal fluid (CSF) provides an invaluable analytical window to the central nervous system (CNS) because it reflects the dynamically changing complement of CNS constituents. We describe an improved method for sampling CSF in rats that is easy to perform. It has a 96% success rate of CSF collection and consistently yields large volumes (150–200 ?l) of CSF. The blood contamination rate is also low (6%) as determined by both visual inspection and the lack of molecular detection of apolipoprotein B, a plasma-derived protein, which is absent in the CNS. This improved method of CSF sampling can have broad applicability in physiological and pharmacological evaluation for diverse CNS targets. We used this technique to provide proof of principle by examining the effect of intraperitoneal insulin on the level of apolipoprotein E (apoE) in the CSF. Insulin (0.5 and 1 U/kg) led to a significant increase of insulin in both plasma and CSF at 2 h after intraperitoneal administration and decreased blood glucose for at least 2 h. ApoE concentrations in CSF, but not in plasma, were also significantly increased, and its time-course was inversely correlated with the alterations in blood glucose over 2 h. These results provide a pharmacological validation of the novel CSF sampling and validation procedure for sampling rat CSF. PMID:22691999

  8. A Proteomic Analysis of Individual and Gender Variations in Normal Human Urine and Cerebrospinal Fluid Using iTRAQ Quantification

    PubMed Central

    Zou, Lili; Wang, Danqi; Shao, Chen; Wang, Yajie; Sun, Wei; Zhang, Liwei

    2015-01-01

    Urine and cerebrospinal fluid (CSF) are two important biofluids used for disease biomarker discovery. For differential proteomic analysis, it is essential to evaluate individual and gender variations. In this study, we characterized urinary and CSF proteomes of 14 healthy volunteers with regard to individual and gender variations using 2DLC-MS/MS analysis and 8-plex iTRAQ quantification. A total of 968/512 urinary/CSF proteins were identified, with 406/280 quantified in all individuals. The median inter-individual coefficients of variation (CVs) were 0.262 and 0.183 for urinary and CSF proteomes, respectively. Cluster analysis showed that male and female urinary proteomes exhibited different patterns, though CSF proteome showed no remarkable gender differences. In comparison with CSF proteome, urinary proteome showed higher individual variation. Further analysis revealed that individual variation was not correlated with protein abundance. The minimum sample size for proteomic analysis with a 2-fold change was 10 (4/5 for males/females using iTRAQ quantification) for urinary or 8 for CSF proteome. Intracellular proteins leaked from exfoliative cells tended to have higher CVs, and extracellular proteins secreted from urinary tract or originating from plasma tended to have lower CVs. The above results might be beneficial for differential proteomic analysis and biomarker discovery. PMID:26222143

  9. Chemotherapy-induced cerebrospinal fluid malabsorption in a shunted child: case report and review of the literature

    PubMed Central

    O'Halloran, Philip J; Kaliaperumal, Chandrasekaran; Caird, John

    2013-01-01

    Ventriculoperitoneal (VP) shunt insertion is one of the most common neurosurgical procedures for the treatment of chronic hydrocephalus. Although regarded as a relatively benign procedure, several complications including obstruction, infection and mechanical failure can be seen during the postoperative stage. Symptomatic sterile cerebrospinal fluid (CSF) ascites and hydrothoracies are rare complications of VP shunt surgery. The paucity of cases makes identifying the aetiological factors difficult, particularly without catheter tip migration. It is most likely that several factors interact to reduce the absorption of CSF. The authors discuss the case of a 5-year-old girl who developed CSF ascites and a pleural effusion after starting chemotherapy for a suprasellar pilocytic astrocytoma, 2?years post-VP shunt insertion, due to a secondary obstructive hydrocephalus. After the initial management of the presenting symptoms, the child's VP shunt was subsequently changed to a ventriculo-atrial shunt and the patient made an unremarkable recovery. We also review the literature pertaining to this rare complication, assessing identifiable risk factors and surgical management options. PMID:23396932

  10. Altered cerebrospinal fluid levels of amyloid ? and amyloid precursor-like protein 1 peptides in Down's syndrome.

    PubMed

    Portelius, Erik; Hölttä, Mikko; Soininen, Hilkka; Bjerke, Maria; Zetterberg, Henrik; Westerlund, Anni; Herukka, Sanna-Kaisa; Blennow, Kaj; Mattsson, Niklas

    2014-06-01

    Down's syndrome (DS) patients develop early Alzheimer's disease pathology with abundant cortical amyloid plaques, likely due to overproduction of the amyloid precursor protein (APP), which subsequently leads to amyloid ? (A?) aggregation. This is reflected in cerebrospinal fluid (CSF) levels of the 42-amino acid long A? peptide (A?1-42), which are increased in young DS patients and decreases with age. However, it is unclear whether DS also affects other aspects of A? metabolism, including production of shorter C- and N-terminal truncated A? peptides, and production of peptides from the amyloid precursor-like protein 1 (APLP1), which is related to APP, and cleaved by the same enzymatic processing machinery. APLP1-derived peptides may be surrogate markers for A?1-42 production in the brain. Here, we used hybrid immunoaffinity-mass spectrometry and enzyme-linked immunosorbent assays to monitor several A? and APLP1 peptides in CSF from DS patients (n = 12) and healthy controls (n = 20). CSF levels of A?1-42 and three endogenous peptides derived from APLP1 (APL1?25, APL1?27 and APL1?28) were decreased in DS compared with controls, while a specific A? peptide, A?1-28, was increased in a majority of the DS individuals. This study indicates that DS causes previously unknown specific alterations of APP and APLP1 metabolism. PMID:24740518

  11. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    PubMed

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  12. Diagnosis and Surgical Management of Traumatic Cerebrospinal Fluid Oculorrhea: Case Report and Systematic Review of the Literature

    PubMed Central

    Pease, Matthew; Marquez, Yvette; Tuchman, Alex; Markarian, Alex; Zada, Gabriel

    2013-01-01

    Background Oculorrhea, or cerebrospinal fluid leakage developing from a cranio-orbital fistula, is a rare development following traumatic injury. Case Report A 22-year-old man involved in a motor vehicle accident developed a blowout fracture of the left orbital roof penetrating the frontal lobe, inducing oculorrhea. He underwent a supraorbital craniotomy for removal of the bony fragment and skull base reconstruction using a pericranial flap. Methods A systematic review of the database was performed to identify all prior cases of traumatic oculorrhea. Results Twenty-two reported cases met inclusion criteria for subsequent analysis. Oculorrhea developed due to blunt and penetrating head injury in 14 (64%) and 8 patients (36%), respectively. The most common mechanisms were car accidents, stab wounds, falls, and gunshot wounds. Ocular signs and symptoms—including visual loss, ophthalmoplegia, and pupillary dysfunction—were commonly associated findings. Initial conservative management was successful in four patients. Thirteen patients underwent initial surgical intervention, and three additional patients required operative intervention following failed conservative treatment. Conclusion Although oculorrhea rarely develops following severe orbital trauma, suspicion should nevertheless be maintained to facilitate more prompt diagnosis and management. The decision for conservative versus surgical management often depends on the severity of the fracture and dural injury. PMID:23943723

  13. Cerebrospinal fluid biomarkers for prognosis of long-term cognitive treatment outcomes in patients with idiopathic normal pressure hydrocephalus.

    PubMed

    Nakajima, Madoka; Miyajima, Masakazu; Ogino, Ikuko; Akiba, Chihiro; Sugano, Hidenori; Hara, Takeshi; Fusegi, Keiko; Karagiozov, Kostadin; Arai, Hajime

    2015-10-15

    The prognosis of cognitive improvement after cerebrospinal fluid (CSF) shunting in idiopathic normal pressure hydrocephalus (iNPH) remains uncertain, with no reports on CSF biomarkers related to long-term cognitive prognosis. We performed a preliminary study of CSF biomarker protein levels for cognitive outcome prognostication of two-year outcomes after shunt treated iNPH in 36 patients (13 women) with a median age of 75years (IQR 69-78). CSF biomarkers included soluble amyloid precursor proteins (sAPP, sAPP?, sAPP?), amyloid ? (A?)1-38, A?1-42 and phosphorylated tau (p-tau), lipocalin-type prostaglandin D synthase (L-PGDS)/?-trace, and cystatin C. The results clearly showed that p-tau levels (sensitivity of 71.4%, specificity of 77.8%, cut-off value of 22.0pg/mL), A?1-38/A?1-42 ratio (77.8%, 81%, 3.58), and the A?1-42/p-tau ratio (76%, 72.7%, 14.6) in preoperative CSF have the potential to determine postoperative prognosis. Improved cognition may be associated with the improvement in CSF circulation after LPS, which likely induces cystatin C and L-PGDS and switches synthesis from A?1-42 to A?1-38. PMID:26169158

  14. Pseudo-Cerebrospinal Fluid Rhinorrhea Resulting from Aberrant Cross-Innervation of Trigeminal and Facial Nerves following Skull Base Surgery

    PubMed Central

    Grannan, Benjamin L.; Linda Bi, Wenya; Dunn, Ian F.

    2015-01-01

    Objectives?Pseudo-cerebrospinal fluid (CSF) rhinorrhea is a rare phenomenon, presumed to result from aberrant autonomic reinnervation of the paranasal mucosa following injury to the greater superficial petrosal nerve or periarterial plexus. In this report, we discuss the case of a postoperative patient with pseudo-CSF rhinorrhea exacerbated by chewing and propose a novel mechanism of pseudo-CSF rhinorrhea. Case Report?A 46-year-old man was found to have mastication-induced unilateral clear rhinorrhea following transtemporal resection of a cerebellopontine angle tumor. Computed tomography cisternogram and ?-2 transferrin analysis proved negative for any evidence of CSF leak. Conclusions?Pseudo-CSF rhinorrhea exacerbated by mastication has not been previously reported in the literature. We propose aberrant cross-innervation of the trigeminal and facial nerves as the mechanism underlying the patient's condition. Pseudo-CSF rhinorrhea is an important entity to identify following skull base surgery because it may spare patients from the unnecessary invasive procedures and morbidity associated with the management of a presumed CSF leak. PMID:26251813

  15. Constructing a statistical atlas of the radii of the optic nerve and cerebrospinal fluid sheath in young healthy adults

    NASA Astrophysics Data System (ADS)

    Harrigan, Robert L.; Plassard, Andrew J.; Mawn, Louise A.; Galloway, Robert L.; Smith, Seth A.; Landman, Bennett A.

    2015-03-01

    Optic neuritis is a sudden inflammation of the optic nerve (ON) and is marked by pain on eye movement, and visual symptoms such as a decrease in visual acuity, color vision, contrast and visual field defects. The ON is closely linked with multiple sclerosis (MS) and patients have a 50% chance of developing MS within 15 years. Recent advances in multi-atlas segmentation methods have omitted volumetric assessment. In the past, measuring the size of the ON has been done by hand. We utilize a new method of automatically segmenting the ON to measure the radii of both the ON and surrounding cerebrospinal fluid (CSF) sheath to develop a normative distribution of healthy young adults. We examine this distribution for any trends and find that ON and CSF sheath radii do not vary between 20-35 years of age and between sexes. We evaluate how six patients suffering from optic neuropathy compare to this distribution of controls. We find that of these six patients, five of them qualitatively differ from the normative distribution which suggests this technique could be used in the future to distinguish between optic neuritis patients and healthy controls

  16. Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants.

    PubMed

    Bruno, Davide; Pomara, Nunzio; Nierenberg, Jay; Ritchie, James C; Lutz, Michael W; Zetterberg, Henrik; Blennow, Kaj

    2012-05-01

    Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE ?4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE ?4. Our results show that the presence of APOE ?4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE ?4 have higher CSF NFL levels than non-?4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of ?4. PMID:21983493

  17. Intraventricular Injection of Noncellular Cerebrospinal Fluid from Subarachnoid Hemorrhage Patient into Rat Ventricles Leads to Ventricular Enlargement and Periventricular Injury.

    PubMed

    Li, Peiliang; Chaudhary, Neeraj; Gemmete, Joseph J; Thompson, B Gregory; Hua, Ya; Xi, Guohua; Pandey, Aditya S

    2016-01-01

    Early brain injury and hydrocephalus (HCP) are important mediators of poor outcome in subarachnoid hemorrhage (SAH) patients. We aim to understand the development of HCP and subependymal cellular injury after intraventricular injection of noncellular human SAH cerebrospinal fluid (CSF) into rat ventricles. Two-hundred microliters of noncellular CSF from SAH patients or normal controls were injected into the right lateral ventricle of seven adult male Sprague-Dawley rats. Propidium iodide (PI) was simultaneously injected to detect necrotic cellular death. Rats were then sacrificed 24 h after surgery and the brain specimens were cut and stained for heme oxygenase 1 (HO-1), an oxidative stress marker. We found that the ventricular area at the bregma level in the CSF injection group was significantly larger than that in the control group (p?

  18. Constructing a statistical atlas of the radii of the optic nerve and cerebrospinal fluid sheath in young healthy adults

    PubMed Central

    Harrigan, Robert L.; Plassard, Andrew J.; Mawn, Louise A.; Galloway, Robert L.; Smith, Seth A.; Landman, Bennett A.

    2015-01-01

    Optic neuritis is a sudden inflammation of the optic nerve (ON) and is marked by pain on eye movement, and visual symptoms such as a decrease in visual acuity, color vision, contrast and visual field defects. The ON is closely linked with multiple sclerosis (MS) and patients have a 50% chance of developing MS within 15 years. Recent advances in multi-atlas segmentation methods have omitted volumetric assessment. In the past, measuring the size of the ON has been done by hand. We utilize a new method of automatically segmenting the ON to measure the radii of both the ON and surrounding cerebrospinal fluid (CSF) sheath to develop a normative distribution of healthy young adults. We examine this distribution for any trends and find that ON and CSF sheath radii do not vary between 20–35 years of age and between sexes. We evaluate how six patients suffering from optic neuropathy compare to this distribution of controls. We find that of these six patients, five of them qualitatively differ from the normative distribution which suggests this technique could be used in the future to distinguish between optic neuritis patients and healthy controls. PMID:25914505

  19. [Phosphorylation of protein kinase C in cerebrospinal fluid-contacting nucleus modulates the inflammatory pain in rats].

    PubMed

    Zhou, Fang; Wang, Jia-You; Tian, En-Qi; Zhang, Li-Cai

    2015-12-25

    The present study was aimed to investigate the role of cerebrospinal fluid-contacting nucleus (CSF-CN) neurons in modulation of inflammatory pain and underlying mechanism. The inflammatory pain model was made by subcutaneous injection of the complete Freund's adjuvant (CFA) into the left hind paw of rats. The phosphorylation level of PKC (p-PKC) was examined by Western blot. Thermal withdrawal latency (TWL) of the rats was measured to assess inflammatory pain. The results showed that, compared with the sham controls, the inflammatory pain model rats showed shortened TWL on day 1, 3, and 7 after CFA injection, as well as increased level of p-PKC in CSF-CN neurons at 24 h after CFA injection. The administration of GF109203X, a PKC inhibitor, into lateral ventricle decreased the level of p-PKC protein expression and increased TWL in the model rats. These results suggest that blocking the PKC pathway in CSF-CN neurons may be an effective way to reduce or eliminate the inflammatory pain. PMID:26701634

  20. Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC-MS/MS.

    PubMed

    Blanco, M E; Encinas, E; González, O; Rico, E; Vozmediano, V; Suárez, E; Alonso, R M

    2015-09-01

    In this study, a selective and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method requiring low sample volume (?100??L) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and (13) C6 -fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for (13) C6 -fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25?ng/mL. Intra- and inter-assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5?µg/kg bolus immediately followed by a 90-min infusion of 3?µg/kg/h). PMID:25755165

  1. Vitamin D Binding Protein Isoforms and Apolipoprotein E in Cerebrospinal Fluid as Prognostic Biomarkers of Multiple Sclerosis

    PubMed Central

    Lis, Katarzyna; Minari, Nicoletta; Falvo, Sara; Marnetto, Fabiana; Caldano, Marzia; Reviglione, Raffaella; Berchialla, Paola; Capobianco, Marco A.; Malentacchi, Maria; Corpillo, Davide; Bertolotto, Antonio

    2015-01-01

    Background Multiple sclerosis (MS) is a multifactorial autoimmune disease of the central nervous system with a heterogeneous and unpredictable course. To date there are no prognostic biomarkers even if they would be extremely useful for early patient intervention with personalized therapies. In this context, the analysis of inter-individual differences in cerebrospinal fluid (CSF) proteome may lead to the discovery of biological markers that are able to distinguish the various clinical forms at diagnosis. Methods To this aim, a two dimensional electrophoresis (2-DE) study was carried out on individual CSF samples from 24 untreated women who underwent lumbar puncture (LP) for suspected MS. The patients were clinically monitored for 5 years and then classified according to the degree of disease aggressiveness and the disease-modifying therapies prescribed during follow up. Results The hierarchical cluster analysis of 2-DE dataset revealed three protein spots which were identified by means of mass spectrometry as Apolipoprotein E (ApoE) and two isoforms of vitamin D binding protein (DBP). These three protein spots enabled us to subdivide the patients into subgroups correlated with clinical classification (MS aggressive forms identification: 80%). In particular, we observed an opposite trend of values for the two protein spots corresponding to different DBP isoforms suggesting a role of a post-translational modification rather than the total protein content in patient categorization. Conclusions These findings proved to be very interesting and innovative and may be developed as new candidate prognostic biomarkers of MS aggressiveness, if confirmed. PMID:26046356

  2. Isolation of dengue serotype 3 virus from the cerebrospinal fluid of an encephalitis patient in Hai Phong, Vietnam in 2013.

    PubMed

    Phu Ly, Minh Huong; Takamatsu, Yuki; Nabeshima, Takeshi; Pham Hoai, Linh Ly; Pham Thi, Hang; Dang Thi, Dinh; Nguyen, Ngoc Linh; Nguyen Thi, Thu Thuy; Le Thi, Quynh Mai; Buerano, Corazon C; Morita, Kouichi; Hasebe, Futoshi

    2015-09-01

    Dengue encephalitis (DE) is characterized as unusual presentation of dengue infection. Despite the reports that DE accounts for only 1-5% of dengue cases, this disease tends to be increasingly reported to threaten global human health throughout dengue endemic areas particularly in Southeast Asia. The molecular information of clinically characterized, neurotropic dengue virus (DENV) in human beings is extremely scarce despite it playing an important role in deciphering the pathogenesis of dengue-related neurological cases. Here we report a case of DE caused by DENV3 genotype III in a male patient with atypical symptoms of DENV infection in Hai Phong, Vietnam in 2013. The virus isolated from the cerebrospinal fluid of this case-patient was closely related to DENV3 genotype III strains isolated from serum of two other patients, who manifested classical dengue in the same year and residing in the same area as the case-patient. It is noteworthy to mention that in 2013, DENV3 genotype III was detected for the first time in Vietnam. PMID:26305828

  3. The blood-cerebrospinal fluid barrier - first evidence for an active transport of organic mercury compounds out of the brain.

    PubMed

    Lohren, Hanna; Bornhorst, Julia; Galla, Hans-Joachim; Schwerdtle, Tanja

    2015-10-01

    Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport. PMID:26267314

  4. Shunt-dependent hydrocephalus following subarachnoid hemorrhage correlates with increased S100B levels in cerebrospinal fluid and serum.

    PubMed

    Brandner, S; Xu, Y; Schmidt, C; Emtmann, Irene; Buchfelder, Michael; Kleindienst, Andrea

    2012-01-01

    Posthemorrhagic hydrocephalus requiring permanent ventriculoperitoneal shunt placement is a major complication of aneurysmal subarachnoid hemorrhage (SAH). High S100B serum and cerebrospinal fluid (CSF) levels are considered to reflect the severity of brain injury. We prospectively assessed whether S100B levels in serum and CSF were predictive parameters for permanent shunt requirement following aneurysmal SAH. In patients suffering from aneurysmal SAH and treated with an external ventricular drain (EVD), S100B levels in serum and CSF were measured daily as long as the EVD was in place. S100B levels of patients who passed their EVD challenge were compared with those patients who required a permanent ventriculoperitoneal shunt placement. Out of 68 patients included in the study, 43 patients (63.2%) passed the EVD challenge and in 25 patients (36.8%) permanent ventriculoperitoneal shunting was performed. Group comparison revealed that in patients who required shunt placement, S100B was significantly higher in CSF (p < 0.05 at days 2, 4, 6, 10; p < 0.005 at days 1, 3, 5, 7, 8, 9) and serum (p < 0.05 at days 4-7) compared with patients who could be weaned from the EVD. Assessment of S100B levels in CSF and serum may be useful as a predictive parameter for shunt dependency in patients with posthemorrhagic hydrocephalus following aneurysmal SAH. PMID:22327696

  5. Descending brain-spinal cord projections in a primitive vertebrate, the lamprey: cerebrospinal fluid-contacting and dopaminergic neurons.

    PubMed

    Barreiro-Iglesias, Antón; Villar-Cerviño, Verona; Anadón, Ramón; Rodicio, María Celina

    2008-12-20

    We used Neurobiotin as a retrograde tract tracer in both larval and adult sea lampreys and observed a number of neuronal brainstem populations (mainly reticular and octaval populations and some diencephalic nuclei) that project to the spinal cord, in agreement with the results of previous tracer studies. We also observed small labeled neurons in the ventral hypothalamus, the mammillary region, and the paratubercular nucleus, nuclei that were not reported as spinal projecting. Notably, most of the labeled cells of the mammillary region and some of the ventral hypothalamus were cerebrospinal fluid-contacting (CSF-c) neurons. Combined tract tracing and immunocytochemistry showed that some of the labeled neurons of the mammillary and paratubercular nuclei were dopamine immunoreactive. In addition, some CSF-c cells were labeled in the caudal rhombencephalon and rostral spinal cord, and many were also dopamine immunoreactive. Results with other tracers (biotinylated dextran amines, horseradish peroxidase, and the carbocyanine dye DiI) also demonstrated that the molecular weight or the molecular nature of the tracer was determinant in revealing diencephalic cells with very thin axons. The results show that descending systems afferent to the spinal cord in lampreys are more varied than previously reported, and reveal a descending projection from CSF-c cells, which is unknown in vertebrates. The present results also reveal the existence of large differences between agnathans and gnathostomes in the organization of the dopaminergic cells that project to the spinal cord. PMID:18925562

  6. Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin.

    PubMed

    Begg, Denovan P; May, Aaron A; Mul, Joram D; Liu, Min; D'Alessio, David A; Seeley, Randy J; Woods, Stephen C

    2015-07-01

    Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake. PMID:25667307

  7. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid cause demyelination of spinal cord explants.

    PubMed

    Blauth, Kevin; Soltys, John; Matschulat, Adeline; Reiter, Cory R; Ritchie, Alanna; Baird, Nicholas L; Bennett, Jeffrey L; Owens, Gregory P

    2015-12-01

    B cells are implicated in the etiology of multiple sclerosis (MS). Intrathecal IgG synthesis, cerebrospinal fluid (CSF) oligoclonal bands and lesional IgG deposition suggest a role for antibody-mediated pathology. We examined the binding of IgG1 monoclonal recombinant antibodies (rAbs) derived from MS patient CSF expanded B cell clones to central nervous system (CNS) tissue. MS rAbs displaying CNS binding to mouse and human CNS tissue were further tested for their ability to induce complement-mediated tissue injury in ex vivo spinal cord explant cultures. The staining of CNS tissue, primary human astrocytes and human neurons revealed a measurable bias in MS rAb binding to antigens preferentially expressed on astrocytes and neurons. MS rAbs that recognize myelin-enriched antigens were rarely detected. Both myelin-specific and some astrocyte/neuronal-specific MS rAbs caused significant myelin loss and astrocyte activation when applied to spinal cord explant cultures in the presence of complement. Overall, the intrathecal B cell response in multiple sclerosis binds to both glial and neuronal targets and produces demyelination in spinal cord explant cultures implicating intrathecal IgG in MS pathogenesis. PMID:26511623

  8. Epidemiology of meningitis due to Haemophilus influenzae type b in children in Bulgaria: a prospective, population-based surveillance study.

    PubMed Central

    Kojouharova, Mira; Gatcheva, Nina; Setchanova, Lena; Robertson, Susan E.; Wenger, Jay D.

    2002-01-01

    OBJECTIVE: To assess the incidence of meningitis caused by Haemophilus influenzae type b (Hib) among children in Bulgaria and to provide evidence for an informed decision on the use of Hib vaccines in Bulgaria. METHODS: From 1 July 1997 to 31 December 1999, active surveillance for meningitis was conducted in six regions. For children with suspected meningitis, a cerebrospinal fluid (CSF) specimen was sent for cytology, chemistry, latex agglutination testing, culture and sensitivity. FINDINGS: During the 2.5-year study period, surveillance was conducted among 138 249 children aged <5 years - a sample representing 40% of all Bulgarian children in this age group. Overall, 285 children with suspected meningitis were identified. In eight children, clinical symptoms of meningitis resolved rapidly before a CSF specimen could be obtained. Of the remaining 277 children, 121 (44%) were classified as having probable bacterial meningitis on the basis of a CSF examination. An organism was identified for 88 (73%) of the 121 cases with probable bacterial meningitis. There were 21 cases of Hib, giving a mean annual incidence of 6.1 Hib meningitis cases per 100 000 children <5 years; the case-fatality rate was 10%. Nearly 60% of Hib isolates were resistant to one or more antibiotics, but they were not resistant to third-generation cephalosporins. CONCLUSION: On the basis of these findings, Hib conjugate vaccines have been included in the list of vaccines recommended for children by the Bulgarian Ministry of Health. The recommended initial treatment for paediatric bacterial meningitis has been changed to third-generation cephalosporins. PMID:12378285

  9. Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study

    PubMed Central

    Westhoff, Dunja; Witlox, Joost; van Aalst, Corneli; Scholtens, Rikie M.; de Rooij, Sophia E.; van Munster, Barbara C.; de Jonghe, Jos F.M.; Houdijk, Alexander P.J.; Eikelenboom, Piet; van Westerloo, David J.; van de Beek, Diederik; van Gool, Willem A.; Koenderman, Leo

    2015-01-01

    Background A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery. Methods Patients (? 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays. Results In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-?-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium. Conclusion Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings. General significance This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling. PMID:26675981

  10. Interaction between SCO-spondin and low density lipoproteins from embryonic cerebrospinal fluid modulates their roles in early neurogenesis

    PubMed Central

    Vera, América; Recabal, Antonia; Saldivia, Natalia; Stanic, Karen; Torrejón, Marcela; Montecinos, Hernán; Caprile, Teresa

    2015-01-01

    During early stages of development, encephalic vesicles are composed by a layer of neuroepithelial cells surrounding a central cavity filled with embryonic cerebrospinal fluid (eCSF). This fluid contains several morphogens that regulate proliferation and differentiation of neuroepithelial cells. One of these neurogenic factors is SCO-spondin, a giant protein secreted to the eCSF from early stages of development. Inhibition of this protein in vivo or in vitro drastically decreases the neurodifferentiation process. Other important neurogenic factors of the eCSF are low density lipoproteins (LDL), the depletion of which generates a 60% decrease in mesencephalic explant neurodifferentiation. The presence of several LDL receptor class A (LDLrA) domains (responsible for LDL binding in other proteins) in the SCO-spondin sequence suggests a possible interaction between both molecules. This possibility was analyzed using three different experimental approaches: (1) Bioinformatics analyses of the SCO-spondin region, that contains eight LDLrA domains in tandem, and of comparisons with the LDL receptor consensus sequence; (2) Analysis of the physical interactions of both molecules through immunohistochemical colocalization in embryonic chick brains and through the immunoprecipitation of LDL with anti-SCO-spondin antibodies; and (3) Analysis of functional interactions during the neurodifferentiation process when these molecules were added to a culture medium of mesencephalic explants. The results revealed that LDL and SCO-spondin interact to form a complex that diminishes the neurogenic capacities that both molecules have separately. Our work suggests that the eCSF is an active signaling center with a complex regulation system that allows for correct brain development. PMID:26074785

  11. The Impact of Spinal Cord Nerve Roots and Denticulate Ligaments on Cerebrospinal Fluid Dynamics in the Cervical Spine

    PubMed Central

    Heidari Pahlavian, Soroush; Yiallourou, Theresia; Tubbs, R. Shane; Bunck, Alexander C.; Loth, Francis; Goodin, Mark; Raisee, Mehrdad; Martin, Bryn A.

    2014-01-01

    Cerebrospinal fluid (CSF) dynamics in the spinal subarachnoid space (SSS) have been thought to play an important pathophysiological role in syringomyelia, Chiari I malformation (CM), and a role in intrathecal drug delivery. Yet, the impact that fine anatomical structures, including nerve roots and denticulate ligaments (NRDL), have on SSS CSF dynamics is not clear. In the present study we assessed the impact of NRDL on CSF dynamics in the cervical SSS. The 3D geometry of the cervical SSS was reconstructed based on manual segmentation of MRI images of a healthy volunteer and a patient with CM. Idealized NRDL were designed and added to each of the geometries based on in vivo measurments in the literature and confirmation by a neuroanatomist. CFD simulations were performed for the healthy and patient case with and without NRDL included. Our results showed that the NRDL had an important impact on CSF dynamics in terms of velocity field and flow patterns. However, pressure distribution was not altered greatly although the NRDL cases required a larger pressure gradient to maintain the same flow. Also, the NRDL did not alter CSF dynamics to a great degree in the SSS from the foramen magnum to the C1 level for the healthy subject and CM patient with mild tonsillar herniation (?6 mm). Overall, the NRDL increased fluid mixing phenomena and resulted in a more complex flow field. Comparison of the streamlines of CSF flow revealed that the presence of NRDL lead to the formation of vortical structures and remarkably increased the local mixing of the CSF throughout the SSS. PMID:24710111

  12. Ventral spinal cerebrospinal fluid leak as the cause of persistent post-dural puncture headache in children.

    PubMed

    Schievink, Wouter I; Maya, M Marcel

    2013-01-01

    Headache occurs after dural puncture in about 1%-25% of children who undergo the procedure-a rate similar to that seen in adults. Persistence of post-dural puncture headache in spite of bed rest, increased fluid intake, and epidural blood patch treatment, however, is rare. The authors reviewed the medical records and imaging studies of all patients 19 years of age or younger who they evaluated between 2001 and 2010 for intracranial hypotension, and they identified 8 children who had persistent post-dural puncture headache despite maximal medical treatment and placement of epidural blood patches. A CSF leak could be demonstrated radiologically and treated surgically in 3 of these patients, and the authors report these 3 cases. The patients were 2 girls (ages 14 and 16 years) who had undergone lumbar puncture for evaluation of headache and fever and 1 boy (age 13 years) who had undergone placement of a lumboperitoneal shunt using a Tuohy needle for treatment of pseudotumor cerebri. The boy also had undergone a laminectomy and exploration of the posterior dural sac, but no CSF leak could be identified. All 3 patients presented with new-onset orthostatic headaches, and in all 3 cases MRI demonstrated a large ventral lumbar or thoracolumbar CSF collection. Conventional myelography or digital subtraction myelography revealed a ventral dural defect at L2-3 requiring surgical repair. Through a posterior transdural approach, the dural defect was repaired using 6-0 Prolene sutures and a dural substitute. Postoperative recovery was uneventful, with complete resolution of orthostatic headache and of the ventral cerebrospinal fluid leak on MRI. The authors conclude that persistent postdural puncture headache requiring surgical repair is rare in children. They note that the CSF leak may be located ventrally and may require conventional or digital subtraction myelography for exact localization and that transdural repair is safe and effective in eliminating the headaches. PMID:23140214

  13. Estimating meningitis hospitalization rates for sentinel hospitals conducting invasive bacterial vaccine-preventable diseases surveillance.

    PubMed

    2013-10-01

    The World Health Organization (WHO)-coordinated Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) sentinel hospital surveillance network provides data for decision making regarding use of pneumococcal conjugate vaccine and Haemophilus influenzae type b (Hib) vaccine, both recommended for inclusion in routine childhood immunization programs worldwide. WHO recommends that countries conduct sentinel hospital surveillance for meningitis among children aged <5 years, including collection of cerebrospinal fluid (CSF) for laboratory detection of bacterial etiologies. Surveillance for pneumonia and sepsis are recommended at selected hospitals with well-functioning laboratories where meningitis surveillance consistently meets process indicators (e.g., surveillance performance indicators). To use sentinel hospital surveillance for meningitis to estimate meningitis hospitalization rates, WHO developed a rapid method to estimate the number of children at-risk for meningitis in a sentinel hospital catchment area. Monitoring changes in denominators over time using consistent methods is essential for interpreting changes in sentinel surveillance incidence data and for assessing the effect of vaccine introduction on disease epidemiology. This report describes the method and its use in The Gambia and Senegal. PMID:24080594

  14. Sodium Butyrate Prevents Memory Impairment by Re-establishing BDNF and GDNF Expression in Experimental Pneumococcal Meningitis.

    PubMed

    Barichello, Tatiana; Generoso, Jaqueline S; Simões, Lutiana R; Faller, Cristiano Julio; Ceretta, Renan A; Petronilho, Fabricia; Lopes-Borges, Jéssica; Valvassori, Samira S; Quevedo, João

    2015-08-01

    Pneumococcal meningitis is a serious infection of the central nervous system (CNS) with high fatality rates that causes reduced psychomotor performance, slight mental slowness, impairments in attention executive functions and learning and memory deficiencies. Previously, we demonstrated a correlation between memory impairment and decreased levels of brain-derived neurotropic factor (BDNF) in the hippocampi of rats subjected to pneumococcal meningitis. Emerging evidence demonstrates that histone acetylation regulates neurotrophins; therefore, a potential molecular intervention against cognitive impairment in bacterial meningitis may be the histone deacetylase (HDAC) inhibitor, sodium butyrate, which stimulates the acetylation of histones and increases BDNF expression. In this study, animals received either artificial cerebrospinal fluid as a placebo or a Streptococcus pneumoniae suspension at a concentration of 5 × 10(9) colony-forming units (CFU/mL). The animals received antibiotic treatment as usual and received saline or sodium butyrate as an adjuvant treatment. Ten days after, meningitis was induced; the animals were subjected to open-field habituation and the step-down inhibitory avoidance task. Immediately after these behavioural tasks, the animals were killed, and their hippocampi were removed to evaluate the expression of BDNF, nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF). In the meningitis group that received saline, the animals presented memory impairment in both behavioural tasks, and hippocampal BDNF and GDNF expression was decreased. Sodium butyrate was able to prevent memory impairment and re-establish hippocampal neurotrophin expression in experimental pneumococcal meningitis. PMID:25284351

  15. Isolation of Cerebrospinal Fluid from Rodent Embryos for use with Dissected Cerebral Cortical Explants

    PubMed Central

    Zappaterra, Mauro W.; LaMantia, Anthony S.; Walsh, Christopher A.; Lehtinen, Maria K.

    2013-01-01

    The CSF is a complex fluid with a dynamically varying proteome throughout development and in adulthood. During embryonic development, the nascent CSF differentiates from the amniotic fluid upon closure of the anterior neural tube. CSF volume then increases over subsequent days as the neuroepithelial progenitor cells lining the ventricles and the choroid plexus generate CSF. The embryonic CSF contacts the apical, ventricular surface of the neural stem cells of the developing brain and spinal cord. CSF provides crucial fluid pressure for the expansion of the developing brain and distributes important growth promoting factors to neural progenitor cells in a temporally-specific manner. To investigate the function of the CSF, it is important to isolate pure samples of embryonic CSF without contamination from blood or the developing telencephalic tissue. Here, we describe a technique to isolate relatively pure samples of ventricular embryonic CSF that can be used for a wide range of experimental assays including mass spectrometry, protein electrophoresis, and cell and primary explant culture. We demonstrate how to dissect and culture cortical explants on porous polycarbonate membranes in order to grow developing cortical tissue with reduced volumes of media or CSF. With this method, experiments can be performed using CSF from varying ages or conditions to investigate the biological activity of the CSF proteome on target cells. PMID:23524481

  16. Cerebrospinal Fluid Enhancement on Fluid Attenuated Inversion Recovery Images After Carotid Artery Stenting with Neuroprotective Balloon Occlusions: Hemodynamic Instability and Blood-Brain Barrier Disruption

    SciTech Connect

    Ogami, Ryo Nakahara, Toshinori; Hamasaki, Osamu; Araki, Hayato; Kurisu, Kaoru

    2011-10-15

    Purpose: A rare complication of carotid artery stenting (CAS), prolonged reversible neurological symptoms with delayed cerebrospinal fluid (CSF) space enhancement on fluid attenuated inversion recovery (FLAIR) images, is associated with blood-brain barrier (BBB) disruption. We prospectively identified patients who showed CSF space enhancement on FLAIR images. Methods: Nineteen patients-5 acute-phase and 14 scheduled-underwent 21 CAS procedures. Balloon catheters were navigated across stenoses, angioplasty was performed using a neuroprotective balloon, and stents were placed with after dilation under distal balloon protection. CSF space hyperintensity or obscuration on FLAIR after versus before CAS indicated CSF space enhancement. Correlations with clinical factors were examined. Results: CSF space was enhanced on FLAIR in 12 (57.1%) cases. Postprocedural CSF space enhancement was significantly related to age, stenosis rate, acute-stage procedure, and total occlusion time. All acute-stage CAS patients showed delayed enhancement. Only age was associated with delayed CSF space enhancement in scheduled CAS patients. Conclusions: Ischemic intolerance for severe carotid artery stenosis and temporary neuroprotective balloon occlusion, causing reperfusion injury, seem to be the main factors that underlie BBB disruption with delayed CSF space enhancement shortly after CAS, rather than sudden poststenting hemodynamic change. Our results suggest that factors related to hemodynamic instability or ischemic intolerance seem to be associated with post-CAS BBB vulnerability. Patients at risk for hemodynamic instability or with ischemic intolerance, which decrease BBB integrity, require careful management to prevent intracranial hemorrhagic and other post-CAS complications.

  17. Analysis of some chosen elements of cerebrospinal fluid and serum in amyotrophic lateral sclerosis patients by total reflection X-ray fluorescence

    NASA Astrophysics Data System (ADS)

    Ostachowicz, B.; Lankosz, M.; Tomik, B.; Adamek, D.; Wobrauschek, P.; Streli, C.; Kregsamer, P.

    2006-11-01

    Trace elements play an important role in the human central nervous system. Significant variations of the concentration of trace elements in body fluids may occur in neurodegenerative diseases. In the present work an investigation of the elemental composition of the serum, and the cerebrospinal fluid in amyotrophic lateral sclerosis patients and a control group was performed. For the analysis of the body fluids Total reflection X-ray Fluorescence (TXRF) spectrometry was used. The samples were taken during routine diagnostic procedures. Na, Mg, Cl, K, Ca, Cu, Zn, and Br were determined in both fluids. In order to validate the results of analysis a serum standard reference material was measured. A t-test was applied to check if the mean concentrations of the elements are different for ALS and the control group. For the serum samples higher values for Br were found in the ALS group, for the cerebrospinal fluid lower values of Na, Mg and Zn as well as higher Ca values were found in the ALS group compared to the control group.

  18. Utility of nonpenetrating titanium clips for dural closure during spinal surgery to prevent postoperative cerebrospinal fluid leakage.

    PubMed

    Ito, Kiyoshi; Aoyama, Tatsuro; Horiuchi, Tetsuyoshi; Hongo, Kazuhiro

    2015-12-01

    OBJECT The nonpenetrating titanium clip has been successfully used in peripheral arterial bypass surgery. The purpose of this study was to evaluate the leakage pressures and patterns of nonpenetrating titanium clips using a simple model that mimicked spinal surgery. In addition, the authors describe their surgical experience with these clips and the follow-up results in 31 consecutive patients. METHODS The authors compared nonpenetrating titanium clips and expanded polytetrafluoroethylene (ePTFE) sutures in relation to the water pressure that could be tolerated by sutured ePTFE sheets, and the leakage pressure patterns were determined. The changes in leakage pressures at 5 minutes, 30 minutes, and 12 hours were examined when the clips and sutures were used in combination with the mesh-and-glue technique in an in vitro study. Thirty-one patients underwent spinal intradural procedures using nonpenetrating titanium clips to suture the dura maters using the meshand-glue technique, involving fibrin glue and polyglycolic acid-fibrin sheets. RESULTS A significant difference was apparent between the ePTFE suture group and the nonpenetrating titanium clip group, with the latter showing a leakage pressure that could be sustained and was 1508% higher than that of the former (p = 0.001). In relation to leakage patterns, the nonpenetrating titanium clips did not make any suture holes in the ePTFE sheet and fluid leakage occurred between the clips, whereas fluid leakage was associated with the pressure elevation that occurred at the suture holes made by the ePTFE sutures. Of the 31 patients who underwent spinal intradural procedures using nonpenetrating titanium clips, 1 (3.2%) experienced cerebrospinal fluid (CSF) leakage postoperatively. No other complications-for example, allergic reactions, adhesions, or infections-were encountered. CONCLUSIONS The interrupted placement of nonpenetrating titanium clips enables dural closure without creating any holes. These clips facilitate improvements in the initial leakage pressure and reduce postoperative CSF leakage following spinal surgery. The authors conclude that it is very beneficial to suture the spinal dura mater using nonpenetrating titanium clips given the anatomical characteristics of the spinal dura mater and the fact that the clips do not create suture holes. PMID:26315957

  19. Implantable device for in-vivo intracranial and cerebrospinal fluid pressure monitoring

    DOEpatents

    Ericson, Milton N. (Knoxville, TN); McKnight, Timothy E. (Greenback, TN); Smith, Stephen F. (London, TN); Hylton, James O. (Clinton, TN)

    2003-01-01

    The present invention relates to a completely implantable intracranial pressure monitor, which can couple to existing fluid shunting systems as well as other internal monitoring probes. The implant sensor produces an analog data signal which is then converted electronically to a digital pulse by generation of a spreading code signal and then transmitted to a location outside the patient by a radio-frequency transmitter to an external receiver. The implanted device can receive power from an internal source as well as an inductive external source. Remote control of the implant is also provided by a control receiver which passes commands from an external source to the implant system logic. Alarm parameters can be programmed into the device which are capable of producing an audible or visual alarm signal. The utility of the monitor can be greatly expanded by using multiple pressure sensors simultaneously or by combining sensors of various physiological types.

  20. Chronic Invasive Aspergillus Sinusitis and Otitis with Meningeal Extension Successfully Treated with Voriconazole.

    PubMed

    Morgand, Marjolaine; Rammaert, Blandine; Poirée, Sylvain; Bougnoux, Marie-Elisabeth; Tran, Hugo; Kania, Romain; Chrétien, Fabrice; Jouvion, Gregory; Lortholary, Olivier

    2015-12-01

    Invasive aspergillosis (IA) is a severe disseminated fungal disease that occurs mostly in immunocompromised patients. However, central nervous system IA, combining meningitis and skull base involvement, does not occur only in groups with classic risk factors for IA; patients with chronic renal failure and diabetes mellitus are also at risk for more chronic forms. In both of our proven IA cases, voriconazole monotherapy was effective without surgery, and cerebrospinal fluid and serum 1,3-?-d-glucan test results were initially positive, in contrast to galactomannan antigen results. PMID:26392507

  1. Appropriate use of the Xpert® MTB/RIF assay in suspected tuberculous meningitis.

    PubMed

    Boyles, T H; Thwaites, G E

    2015-03-01

    We disagree with the recommendation by the World Health Organization to use Xpert(®) MTB/RIF on cerebrospinal fluid for the initial diagnosis of tuberculous meningitis (TBM). TBM is a devastating disease requiring empirical treatment even when the probability of disease is low. We suggest that a useful TBM diagnostic test needs a negative predictive value (NPV) of ? 99% so that empirical treatment can be stopped safely. The NPV of Xpert is around 84%, making a negative test of limited value. While better tests are awaited, a composite score, possibly combining Xpert with clinical variables and with high NPV, should be constructed and validated prospectively. PMID:25686133

  2. A Rare Case of Ibuprofen-Induced Eosinophilic Meningitis in a 13-Year-Old Girl

    PubMed Central

    Bansal, Sharad; Gupta, Mukesh; Sharma, Deepak; Bansal, Shweta

    2014-01-01

    Eosinophilic meningoencephalitis is based on clinical manifestations and microscopic identification of eosinophils present in cerebrospinal fluid (CSF). It is caused by a variety of helminthic infections with most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Many case reports are there in which parasites have been found responsible, but there are rare reports of CSF eosinophilia associated with the use of drugs. We report a case of drug-induced (ibuprofen) eosinophilic meningitis in a healthy female who presented to us with severe headache and improved dramatically after drug withdrawal. PMID:24596473

  3. High Resolution Discovery Proteomics Reveals Candidate Disease Progression Markers of Alzheimer’s Disease in Human Cerebrospinal Fluid

    PubMed Central

    Lee, Anita Y. H.; Song, Qinghua; Liaw, Andy; Wiener, Matt; Paweletz, Cloud P.; Seeburger, Jeffrey L.; Li, Jenny; Meng, Fanyu; Deyanova, Ekaterina G.; Mazur, Matthew T.; Settlage, Robert E.; Zhao, Xuemei; Southwick, Katie; Du, Yi; Holder, Dan; Sachs, Jeffrey R.; Laterza, Omar F.; Dallob, Aimee; Chappell, Derek L.; Snyder, Karen; Modur, Vijay; King, Elizabeth; Joachim, Catharine; Bondarenko, Andrey Y.; Shearman, Mark; Soper, Keith A.; Smith, A. David; Potter, William Z.; Koblan, Ken S.; Sachs, Alan B.

    2015-01-01

    Disease modifying treatments for Alzheimer’s disease (AD) constitute a major goal in medicine. Current trends suggest that biomarkers reflective of AD neuropathology and modifiable by treatment would provide supportive evidence for disease modification. Nevertheless, a lack of quantitative tools to assess disease modifying treatment effects remains a major hurdle. Cerebrospinal fluid (CSF) biochemical markers such as total tau, p-tau and Ab42 are well established markers of AD; however, global quantitative biochemical changes in CSF in AD disease progression remain largely uncharacterized. Here we applied a high resolution open discovery platform, dMS, to profile a cross-sectional cohort of lumbar CSF from post-mortem diagnosed AD patients versus those from non-AD/non-demented (control) patients. Multiple markers were identified to be statistically significant in the cohort tested. We selected two markers SME-1 (p<0.0001) and SME-2 (p = 0.0004) for evaluation in a second independent longitudinal cohort of human CSF from post-mortem diagnosed AD patients and age-matched and case-matched control patients. In cohort-2, SME-1, identified as neuronal secretory protein VGF, and SME-2, identified as neuronal pentraxin receptor-1 (NPTXR), in AD were 21% (p = 0.039) and 17% (p = 0.026) lower, at baseline, respectively, than in controls. Linear mixed model analysis in the longitudinal cohort estimate a decrease in the levels of VGF and NPTXR at the rate of 10.9% and 6.9% per year in the AD patients, whereas both markers increased in controls. Because these markers are detected by mass spectrometry without the need for antibody reagents, targeted MS based assays provide a clear translation path for evaluating selected AD disease-progression markers with high analytical precision in the clinic. PMID:26270474

  4. Bypassing hazard of housekeeping genes: their evaluation in rat granule neurons treated with cerebrospinal fluid of multiple sclerosis subjects.

    PubMed

    Mathur, Deepali; Urena-Peralta, Juan R; Lopez-Rodas, Gerardo; Casanova, Bonaventura; Coret-Ferrer, Francisco; Burgal-Marti, Maria

    2015-01-01

    Gene expression studies employing real-time PCR has become an intrinsic part of biomedical research. Appropriate normalization of target gene transcript(s) based on stably expressed housekeeping genes is crucial in individual experimental conditions to obtain accurate results. In multiple sclerosis (MS), several gene expression studies have been undertaken, however, the suitability of housekeeping genes to express stably in this disease is not yet explored. Recent research suggests that their expression level may vary under different experimental conditions. Hence it is indispensible to evaluate their expression stability to accurately normalize target gene transcripts. The present study aims to evaluate the expression stability of seven housekeeping genes in rat granule neurons treated with cerebrospinal fluid of MS patients. The selected reference genes were quantified by real time PCR and their expression stability was assessed using GeNorm and NormFinder algorithms. GeNorm identified transferrin receptor (Tfrc) and microglobulin beta-2 (B2m) the most stable genes followed by ribosomal protein L19 (Rpl19) whereas ?-actin (ActB) and glyceraldehyde-3-phosphate-dehydrogenase (Gapdh) the most fluctuated ones in these neurons. NormFinder identified Tfrc as the best invariable gene followed by B2m and Rpl19. ActB and Gapdh were the least stable genes as analyzed by NormFinder algorithm. Both methods reported Tfrc and B2m the most stably expressed genes and Gapdh the least stable one. Altogether our data demonstrate the significance of pre-validation of housekeeping genes for accurate normalization and indicates Tfrc and B2m as best endogenous controls in MS. ActB and Gapdh are not recommended in gene expression studies related to current one. PMID:26441545

  5. Photoperiod affects the cerebrospinal fluid proteome: a comparison between short day- and long day-treated ewes.

    PubMed

    Teixeira-Gomes, A-P; Harichaux, G; Gennetay, D; Skipor, J; Thiery, J-C; Labas, V; Dufourny, L

    2015-10-01

    Photoperiod is the main physical synchronizer of seasonal functions and a key factor in the modulation of molecule access to cerebrospinal fluid (CSF) in animals. Previous work has shown that photoperiod affects the transfer rate of steroids and protein hormones from blood to CSF and modulates choroid plexus tight junction protein content. We hypothesized that the CSF proteome would also be modified by photoperiod. We tested this hypothesis by comparing CSF obtained from the third ventricle of mature, ovariectomized, estradiol-replaced ewes exposed to long day length (LD) or short day length (SD). Variations in CSF protein expression between SD- or LD-treated ewes were studied in pools of CSF collected for 48 h. Proteins were precipitated, concentrated, and included in a polyacrylamide gel without protein fractionation. After in-gel tryptic digestion of total protein samples, we analyzed the resulting peptides by nanoliquid chromatography coupled with high-resolution tandem mass spectrometry (GeLC-MS/MS). Quantitative analysis was performed using 2 methods based on spectral counting and extracted ion chromatograms. Among 103 identified proteins, 41 were differentially expressed between LD and SD ewes (with P < 0.05 and at least a 1.5-fold difference). Of the 41 differentially expressed proteins, 22 were identified by both methods and 19 using extracted ion chromatograms only. Eighteen proteins were more abundant in LD ewes and 23 were more abundant in SD ewes. These proteins are involved in numerous functions including hormone transport, immune system activity, metabolism, and angiogenesis. To confirm proteomic results, 2 proteins, pigment epithelium-derived factor (PEDF) and gelsolin, for each individual sample of CSF collected under SD or LD were analyzed with Western blots. These results suggest an important photoperiod-dependent change in CSF proteome composition. Nevertheless, additional studies are required to assess the role of each protein in seasonal functions. PMID:26046803

  6. Population Pharmacokinetics of Meropenem in Plasma and Cerebrospinal Fluid of Infants with Suspected or Complicated Intra-Abdominal Infections

    PubMed Central

    SMITH, P. BRIAN; COHEN-WOLKOWIEZ, MICHAEL; CASTRO, LISA M.; POINDEXTER, BRENDA; BIDEGAIN, MARGARITA; WEITKAMP, JOERN-HENDRIK; SCHELONKA, ROBERT L.; WARD, ROBERT M.; WADE, KELLY; VALENCIA, GLORIA; BURCHFIELD, DAVID; ARRIETA, ANTONIO; BHATT-MEHTA, VARSHA; WALSH, MICHELE; KANTAK, ANAND; RASMUSSEN, MAYNARD; SULLIVAN, JANICE E.; FINER, NEIL; BROZANSKI, BEVERLY S.; SANCHEZ, PABLO; ANKER, JOHN VAN DEN; BLUMER, JEFFREY; KEARNS, GREGORY L.; CAPPARELLI, EDMUND V.; ANAND, RAVINDER; BENJAMIN, DANIEL K.

    2011-01-01

    Background Suspected or complicated intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial agent with excellent activity against pathogens associated with intra-abdominal infections in this population. The purpose of this study was to determine the pharmacokinetics (PK) of meropenem in young infants as a basis for optimizing dosing and minimizing adverse events. Methods Premature and term infants <91 days of age hospitalized in 24 neonatal intensive care units were studied. Limited PK sampling was performed following single and multiple doses of meropenem 20–30 mg/kg of body weight every 8–12 hours based on postnatal and gestational age at birth. Population and individual patient (Bayesian) PK parameters were estimated using NONMEM®. Results Two hundred infants were enrolled and received study drug. One hundred eighty-eight infants with 780 plasma meropenem concentrations were analyzed. Their median (range) gestational age at birth and postnatal age at PK evaluation were 28 (23–40) weeks and 21 (1–92) days, respectively. In the final PK model, meropenem clearance (CL) was strongly associated with serum creatinine (SCR) and postmenstrual age (PMA) (CL [L/h/kg] = 0.12*[(0.5/SCR)**0.27]*[(PMA/32.7)**1.46]). Meropenem concentrations remained >4 ?g/mL for 50% of the dose interval and >2 ?g/mL for 75% of the dose interval in 96% and 92% of patients, respectively. The estimated penetration of meropenem into the cerebrospinal fluid was 70% (5–148). Conclusions Meropenem dosing strategies based on postnatal and gestational age achieved therapeutic drug exposure in almost all infants. PMID:21829139

  7. Cerebrospinal Fluid ?-Synuclein and Lewy Body-Like Symptoms in Normal Controls, Mild Cognitive Impairment, and Alzheimer’s Disease

    PubMed Central

    Mackin, R. Scott; Insel, Philip; Zhang, Jing; Mohlenhoff, Brian; Galasko, Douglas; Weiner, Michael; Mattsson, Niklas

    2015-01-01

    Background Reduced cerebrospinal fluid (CSF) ?-synuclein has been described in synucleinopathies, including dementia with Lewy bodies (DLB). Common symptoms of DLB include visual hallucinations and visuospatial and executive deficits. Co-occurrence of Lewy body pathology is common in Alzheimer’s disease (AD) patients, but it is unknown if reduced CSF ?-synuclein is associated with Lewy body-like symptomatology in AD. Objective Determine associations between CSF ?-synuclein and Lewy body-like symptomatology. Methods We included 73 controls (NC), 121 mild cognitive impairment (MCI) patients, and 61 AD patients (median follow-up 3.5 years, range 0.6–7.8). We tested associations between baseline CSF ?-synuclein and visual hallucinations and (longitudinal) cognition. Models were tested with and without co-varying for CSF total tau (T-tau), which is elevated in AD patients, and believed to reflect neurodegeneration. Results Hallucinations were reported in 20% of AD patients, 13% of MCI patients, and 8% of NC. In AD, low CSF ?-synuclein was associated with hallucinations. When adjusting for CSF T-tau, low CSF ?-synuclein was associated with accelerated decline of executive function (NC, MCI, and AD), memory (MCI and AD), and language (MCI). Conclusion The associations of low CSF ?-synuclein with hallucinations and poor executive function, which are hallmarks of DLB, indirectly suggest that this biomarker may reflect underlying synuclein pathology. The associations with memory and language in MCI and AD suggests either that reduced CSF ?-synuclein also partly reflects global impaired neuronal/synaptic function, or that non-specific overall cognitive deterioration is accelerated in the presence of synuclein related pathology. The findings will require autopsy verification. PMID:25125463

  8. New experimental model of acute aqueductal blockage in cats: effects on cerebrospinal fluid pressure and the size of brain ventricles.

    PubMed

    Klarica, M; Oreskovi?, D; Bozi?, B; Vuki?, M; Butkovi?, V; Bulat, M

    2009-02-18

    It is generally assumed that cerebrospinal fluid (CSF) is secreted in the brain ventricles, and so after an acute blockage of the aqueduct of Sylvius an increase in the ventricular CSF pressure and dilation of isolated ventricles may be expected. We have tested this hypothesis in cats. After blocking the aqueduct, we measured the CSF pressure in both isolated ventricles and the cisterna magna, and performed radiographic monitoring of the cross-sectional area of the lateral ventricle. The complete aqueductal blockage was achieved by implanting a plastic cannula into the aqueduct of Sylvius through a small tunnel in the vermis of the cerebellum in the chloralose-anesthetized cats. After the reconstitution of the occipital bone, the CSF pressure was measured in the isolated ventricles via a plastic cannula implanted in the aqueduct of Sylvius and in the cisterna magna via a stainless steel cannula. During the following 2 h, the CSF pressures in the isolated ventricles and cisterna magna were identical to those in control conditions. We also monitored the ventricular cross-sectional area by means of radiography for 2 h after the aqueductal blockage and failed to observe any significant changes. When mock CSF was infused into isolated ventricles to imitate the CSF secretion, the gradient of pressure between the ventricle and cisterna magna developed, and disappeared as soon as the infusion was terminated. However, when mock CSF was infused into the cisterna magna at various rates, the resulting increased subarachnoid CSF pressure was accurately transmitted across the brain parenchyma into the CSF of isolated ventricles. The lack of the increase in the CSF pressure and ventricular dilation during 2 h of aqueductal blockage suggests that aqueductal obstruction by itself does not lead to development of hypertensive acute hydrocephalus in cats. PMID:19111908

  9. Cerebrospinal fluid biomarkers for Alzheimer’s disease: the role of apolipoprotein E genotype, age, and sex

    PubMed Central

    Mehrabian, Shima; Alexopoulos, Panagiotis; Ortner, Marion; Traykov, Latchezar; Grimmer, Timo; Kurz, Alexander; Förstl, Hans; Bickel, Horst; Diehl-Schmid, Janine

    2015-01-01

    Introduction Cerebrospinal fluid (CSF) biomarkers improve the diagnostic accuracy for Alzheimer’s disease (AD), even at the predementia stage of the disease. The ?4-allele of apolipoprotein E (ApoE ?4), female sex, and older age are well-known risk factors for AD. It is unclear how these risk factors affect the CSF biomarkers in patients with AD. Aim The objective of this study was to investigate the associations of ApoE ?4, sex, and age with CSF biomarker levels in a unicenter sample of patients with AD that includes a high proportion of patients with early-onset AD (EOAD). Methods The CSF levels of amyloid-? 1-42 (A?1-42) and total-tau of 117 subjects with mild to moderate AD (55 late-onset AD and 62 EOAD) were assessed. All subjects underwent ApoE genotyping, clinical evaluation, comprehensive neuropsychological assessments, and neuroimaging. Associations between CSF biomarker levels, ApoE ?4 allele frequency, age, and sex were evaluated. Results In the whole patient sample and in the late-onset AD subgroup ?4 homozygous subjects had significantly lower CSF A?1-42 levels compared with ?4 heterozygous subjects and ?4 noncarriers. This association was not detected in the EOAD group. Age group, sex, and severity of cognitive decline did not have a significant impact on CSF A?1-42 levels. No significant associations were found between ApoE ?4 allele frequency and CSF total-tau levels. Conclusion ApoE ?4 allele is associated with a reduction of CSF A?1-42 levels. This result is consistent with the findings of several previous studies. In the subgroup of patients with EOAD this association was not replicated. Larger studies are necessary to further investigate associations between ApoE ?4 allele frequency and CSF biomarker levels in patients with EOAD. PMID:26719695

  10. Risk Factors in Chronic Subdural Hematoma: Comparison of Irrigation with Artificial Cerebrospinal Fluid and Normal Saline in a Cohort Analysis

    PubMed Central

    Adachi, Akihiko; Higuchi, Yoshinori; Fujikawa, Atsushi; Machida, Toshio; Sueyoshi, Shigeo; Harigaya, Kenichi; Ono, Junichi; Saeki, Naokatsu

    2014-01-01

    Background Chronic subdural hematoma (CSDH) is known to have a substantial recurrence rate. Artificial cerebrospinal fluid (ACF) is an effective irrigation solution in general open craniotomy and endoneurosurgery, but no evidence of its use in burr-hole surgery exists. Objective To identify the potential of ACF irrigation to prevent CSDH recurrence. More specifically, to investigate the perioperative and intraoperative prognostic factors, and to identify controllable ones. Methods To examine various prognostic factors, 120 consecutive patients with unilateral CSDH treated with burr-hole drainage between September 2007 and March 2013 were analyzed. Intraoperative irrigation was performed with one of two irrigation solutions: normal saline (NS; n?=?60) or ACF (n?=?60). All patients were followed-up for at least 6 months postoperatively. We also examined the morphological alternations of the hematoma outer membranes after incubation with different solutions. Results Eleven patients (9.2%) had recurrence. Nine patients (15%) required additional surgery in the NS group, whereas only 2 patients (3.3%) in the ACF group required additional surgery. Among preoperative and intraoperative data, age (<80 years old, P?=?.044), thrombocyte (>22.0, P?=?.037), laterality (right, P?=?.03), and irrigation solution (ACF, P?=?.027) were related to smaller recurrence rates by log-rank tests. Only the type of irrigation solution used significantly correlated with recurrence in favor of ACF in both Cox proportional hazards (relative hazard: 0.20, 95% confidence interval (CI): 0.04–0.99; P?=?.049) and logistic regression models (odds ratio, 0.17, 95% CI: 0.03–0.92; P?=?.04) using these factors. Histological examinations of the hematoma membranes showed that the membranes incubated with NS were loose and infiltrated by inflammatory cells compared with those incubated with ACF. Conclusion Irrigation with ACF decreased the rate of CSDH recurrence. PMID:25089621

  11. Autoantibody Profiling on Human Proteome Microarray for Biomarker Discovery in Cerebrospinal Fluid and Sera of Neuropsychiatric Lupus

    PubMed Central

    Song, Guang; Li, Ping; Shan, Qiang; Zhang, Xuan; Zhang, Fengchun; Zhu, Heng; Wu, Lin; Li, Yongzhe

    2015-01-01

    Autoantibodies in cerebrospinal fluid (CSF) from patients with neuropsychiatric systemic lupus erythematosus (NPSLE) may be potential biomarkers for prediction, diagnosis, or prognosis of NPSLE. We used a human proteome microarray with~17,000 unique full-length human proteins to investigate autoantibodies associated with NPSLE. Twenty-nine CSF specimens from 12 NPSLE, 7 non-NPSLE, and 10 control (non-systemic lupus erythematosus)patients were screened for NPSLE-associated autoantibodies with proteome microarrays. A focused autoantigen microarray of candidate NPSLE autoantigens was applied to profile a larger cohort of CSF with patient-matched sera. We identified 137 autoantigens associated with NPSLE. Ingenuity Pathway Analysis revealed that these autoantigens were enriched for functions involved in neurological diseases (score = 43).Anti-proliferating cell nuclear antigen (PCNA) was found in the CSF of NPSLE and non-NPSLE patients. The positive rates of 4 autoantibodies in CSF specimens were significantly different between the SLE (i.e., NPSLE and non-NPSLE) and control groups: anti-ribosomal protein RPLP0, anti-RPLP1, anti-RPLP2, and anti-TROVE2 (also known as anti-Ro/SS-A). The positive rate for anti-SS-A associated with NPSLE was higher than that for non-NPSLE (31.11% cf. 10.71%; P = 0.045).Further analysis showed that anti-SS-A in CSF specimens was related to neuropsychiatric syndromes of the central nervous system in SLE (P = 0.009). Analysis with Spearman’s rank correlation coefficient indicated that the titers of anti-RPLP2 and anti-SS-A in paired CSF and serum specimens significantly correlated. Human proteome microarrays offer a powerful platform to discover novel autoantibodies in CSF samples. Anti-SS-A autoantibodies may be potential CSF markers for NPSLE. PMID:25954975

  12. JC virus load in cerebrospinal fluid and transcriptional control region rearrangements may predict the clinical course of progressive multifocal leukoencephalopathy

    PubMed Central

    Delbue, Serena; Elia, Francesca; Carloni, Camilla; Tavazzi, Eleonora; Marchioni, Enrico; Carluccio, Silvia; Signorini, Lucia; Novati, Stefano; Maserati, Renato; Ferrante, Pasquale

    2012-01-01

    Progressive multifocal leukoencephalopathy (PML) is a severe disease of the central nervous system (CNS), caused by infection with the Polyomavirus JC virus (JCV). Because there are no known treatments or prognostic factors, we performed a long-term study focusing mainly on cerebrospinal fluid (CSF) samples from PML patients to describe the virological features akin to the different forms of the disease. Twenty-eight PML patients were enrolled: 10 HIV-1+ patients with classical PML (CPML), 9 HIV-1+ patients with slowly progressing or stable neurological symptoms (benign PML), 3 HIV-1+ asymptomatic patients and 6 HIV-1-negative patients. CSF, urine and blood samples were collected at the enrollment (baseline) and every six months afterwards when possible. The JCV DNA and HIV-1 RNA loads were determined, and the JCV strains were characterized. At baseline , the mean CSF JCV load was log 6.0 ± 1.2 copies/ml for CPML patients, log 4.0 ± 1.0 copies/ml for benign PML patients, log 4.2 ± 0.5 copies/ml for asymptomatic PML patients and log 5.8 ± 1.3 copies/ml for HIV-1-negative PML patients (CPML versus benign: p<0.01; CPML versus asymptomatic: p<0.05; HIV-1 negative versus benign: p<0.01). Organization of the JCV transcriptional control region (TCR) showed unusual archetype structures in 2 long-term survival patients; the NF1 sequence was found most commonly, whereas the Sp1 binding site was the most common for both CPML patients and HIV-1 negative patients. Our results suggest that the JCV load in the CSF and the organization of the TCR should be considered as indicators of PML clinical outcome. PMID:22253012

  13. IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia.

    PubMed

    Severance, Emily G; Gressitt, Kristin L; Alaedini, Armin; Rohleder, Cathrin; Enning, Frank; Bumb, J Malte; Müller, Juliane K; Schwarz, Emanuel; Yolken, Robert H; Leweke, F Markus

    2015-02-01

    Schizophrenia is a complex brain disorder that may be accompanied by idiopathic inflammation. Classic central nervous system (CNS) inflammatory disorders such as viral encephalitis or multiple sclerosis can be characterized by incongruent serum and cerebrospinal fluid (CSF) IgG due in part to localized intrathecal synthesis of antibodies. The dietary antigens, wheat gluten and bovine milk casein, can induce a humoral immune response in susceptible individuals with schizophrenia, but the correlation between the food-derived serological and intrathecal IgG response is not known. Here, we measured IgG to wheat gluten and bovine milk casein in matched serum and CSF samples from 105 individuals with first-episode schizophrenia (n=75 antipsychotic-naïve), and 61 controls. We found striking correlations in the levels of IgG response to dietary proteins between serum and CSF of schizophrenia patients, but not controls (schizophrenia, R(2)=0.34-0.55, p?0.0001; controls R(2)=0.05-0.06, p>0.33). A gauge of blood-CSF barrier permeability and CSF flow rate, the CSF-to-serum albumin ratio, was significantly elevated in cases compared to controls (p?0.001-0.003). Indicators of intrathecal IgG production, the CSF IgG index and the specific Antibody Index, were not significantly altered in schizophrenia compared to controls. Thus, the selective diffusion of bovine milk casein and wheat gluten antibodies between serum and CSF in schizophrenia may be the function of a low-level anatomical barrier dysfunction or altered CSF flow rate, which may be transient in nature. PMID:25241021

  14. Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves

    PubMed Central

    Abeysekara, Saman; Zello, Gordon A.; Lohmann, Katharina L.; Alcorn, Jane; Hamilton, Don L.; Naylor, Jonathan M.

    2012-01-01

    In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO3) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± Sx) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco2, torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco2 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco2 and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco2 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis. PMID:22754090

  15. Comparison of cerebrospinal fluid biomarkers between idiopathic normal pressure hydrocephalus and subarachnoid hemorrhage-induced chronic hydrocephalus: A pilot study

    PubMed Central

    Lee, Jeong-Hyun; Park, Dong-Hyuk; Back, Dong-Bin; Lee, Jea-Young; Lee, Chang-In; Park, Kyung-Jae; Kang, Shin-Hyuk; Cho, Tai-Hyoung; Chung, Yong-Gu

    2012-01-01

    Summary Background We examined the cerebrospinal fluid (CSF) markers of subarachnoid hemorrhage (SAH)-induced and idiopathic normal pressure hydrocephalus (INPH) to investigate the pathophysiology and mechanism of communicating hydrocephalus compared to obstructive hydrocephalus. Material/Methods We obtained CSF samples from 8 INPH, 10 SAH-induced hydrocephalus, and 6 unmatched patients with non-hemorrhagic obstructive hydrocephalus during their ventriculoperitoneal shunt operations. Transforming growth factor (TGF)-?1, tumor necrosis factor (TNF)-?, vascular endothelial growth factor (VEGF), and total tau in the CSF were analyzed via enzyme-linked immunosorbent assay. Results The mean VEGF levels in the CSF of patients with SAH-induced hydrocephalus, INPH, and obstructive hydrocephalus were 239±131, 239±75, and 163±122 pg/mL, respectively. The total tau concentrations in the CSF of the groups were 1139±1900, 325±325, and 1550±2886 pg/mL, respectively. TNF-? values were 114±34, 134±38, and 55±16 pg/mL, respectively. TGF-?1 values were 953±430, 869±447, and 136±63 pg/mL, respectively. A significant difference in TNF-? and TGF-?1 levels was observed only between SAH-induced and chronic obstructive hydrocephalus, and between INPH and chronic obstructive hydrocephalus (p<0.01). Conclusions No significant differences in the 4 CSF biomarker levels were observed between INPH and SAH-induced hydrocephalus, whereas CSF TNF-? and TGF-?1 levels were increased compared to those in patients with chronic obstructive hydrocephalus. Post-SAH hydrocephalus and INPH are probably more destructive to neural tissues, and then stimulate the inflammatory reaction and healing process, compared with obstructive hydrocephalus. PMID:23197244

  16. Microscopic Particles in Two Fractions of Fresh Cerebrospinal Fluid in Twins with Schizophrenia or Bipolar Disorder and in Healthy Controls

    PubMed Central

    Johansson, Viktoria; Nybom, Rolf; Wetterberg, Lennart; Hultman, Christina M.; Cannon, Tyrone D.; Johansson, Anette G. M.; Ekman, Carl Johan; Landén, Mikael

    2012-01-01

    Background Using scanning electron microscopy, microscopic structures have been identified in fresh cerebrospinal fluid (CSF) in patients with schizophrenia and bipolar disorder, but only rarely in control subjects. However, it has not been determined whether these microscopic particles represent state or trait markers, i.e. if their presence is related to clinical manifestations of the disease or if they also can be found in as yet asymptomatic individuals with a genetic liability. This question can be addressed by studying twins discordant or concordant for schizophrenia or bipolar disorder. Methodology/Principal Findings We investigated microscopic structures in CSF in 102 individuals: 21 monozygotic and 16 dizygotic twins affected or not affected with schizophrenia, schizoaffective disorder or bipolar disorder and in 65 healthy singleton controls. A first and a second fraction of CSF was freshly applied on filters and examined by scanning electron microscopy technique. Spherical particles with lipid appearance averaging between 0.1 to 8.0 µm in diameter were detected in the center of the filter as well as located in the margins of larger aggregates binding in a viscous state. Structures were found in 12 of 17 probands, 5 of 12 healthy co-twins and 3 of 73 healthy controls. Thus, a positive microscopic finding significantly increased the likelihood of belonging to the proband group (OR?=?48, 95% CL: 8.2–550, p<0.0001) and the co-twin-group (OR?=?16, 95% CL: 2.0–218, p?=?0.006). Age, sex, history of alcohol abuse or anxiety syndrome, somatic disorder and markers of acute inflammatory activity did not account for group differences; nor did exposure to psychotropic medication. Conclusion Presence of microscopic particles in CSF may possibly reflect trait dependent genetic or environmental vulnerability in patients with schizophrenia, schizoaffective disorder or bipolar disorder. PMID:23049916

  17. Expression and Transport of ?-Synuclein at the Blood-Cerebrospinal Fluid Barrier and Effects of Manganese Exposure

    PubMed Central

    Bates, Christopher A.; Fu, Sherleen; Ysselstein, Daniel; Rochet, Jean-Christophe; Zheng, Wei

    2015-01-01

    The choroid plexus maintains the homeostasis of critical molecules in the brain by regulating their transport between the blood and cerebrospinal fluid (CSF). The current study was designed to investigate the potential role of the blood-CSF barrier (BCSFB) in ?-synuclein (a-Syn) transport in the brain as affected by exposure to manganese (Mn), the toxic metal implicated in Parkinsonian disorders. Immunohistochemistry was used to identify intracellular a-Syn expression at the BCSFB. Quantitative real-time PCR was used to quantify the change in a-Syn mRNA expression following Mn treatments at the BCSFB in vitro. ELISA was used to quantify a-Syn levels following in vivo and in vitro treatments of Mn, copper (Cu), and/or external a-Syn. Thioflavin-T assay was used to investigate a-Syn aggregation after incubating with Mn and/or Cu in vitro. A two-chamber Transwell system was used to study a-Syn transport by BCSFB monolayer. Data revealed the expression of endogenous a-Syn in rat choroid plexus tissue and immortalized choroidal epithelial Z310 cells. The cultured primary choroidal epithelia from rats showed the ability to take up a-Syn from extracellular medium and transport a-Syn across the cellular monolayer from the donor to receiver chamber. Exposure of cells with Mn induced intracellular a-Syn accumulation without causing any significant changes in a-Syn mRNA expression. A significant increase in a-Syn aggregation in a cell-free system was observed with the presence of Mn. Moreover, Mn exposure resulted in a significant uptake of a-Syn by primary cells. These data indicate that the BCSFB expresses a-Syn endogenously and is capable of transporting a-Syn across the BCSFB monolayer; Mn exposure apparently increases a-Syn accumulation in the BCSFB by facilitating its uptake and intracellular aggregation.

  18. Cerebrospinal Fluid (CSF) 25-Hydroxyvitamin D Concentration and CSF Acetylcholinesterase Activity Are Reduced in Patients with Alzheimer's Disease

    PubMed Central

    Johansson, Per; Almqvist, Erik G.; Johansson, Jan-Ove; Mattsson, Niklas; Andreasson, Ulf; Hansson, Oskar; Wallin, Anders; Blennow, Kaj; Zetterberg, Henrik; Svensson, Johan

    2013-01-01

    Background Little is known of vitamin D concentration in cerebrospinal fluid (CSF) in Alzheimer´s disease (AD) and its relation with CSF acetylcholinesterase (AChE) activity, a marker of cholinergic function. Methods A cross-sectional study of 52 consecutive patients under primary evaluation of cognitive impairment and 17 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI) diagnosed with AD dementia upon follow-up (n = 28), other dementias (n = 12), and stable MCI (SMCI, n = 12). We determined serum and CSF concentrations of calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and CSF activities of AChE and butyrylcholinesterase (BuChE). Findings CSF 25OHD level was reduced in AD patients (P < 0.05), and CSF AChE activity was decreased both in patients with AD (P < 0.05) and other dementias (P < 0.01) compared to healthy controls. None of the measured variables differed between BuChE K-variant genotypes whereas the participants that were homozygous in terms of the apolipoprotein E (APOE) ?4 allele had decreased CSF AChE activity compared to subjects lacking the APOE ?4 allele (P = 0.01). In AD patients (n=28), CSF AChE activity correlated positively with CSF levels of total tau (T-tau) (r = 0.44, P < 0.05) and phosphorylated tau protein (P-tau) (r = 0.50, P < 0.01), but CSF activities of AChE or BuChE did not correlate with serum or CSF levels of 25OHD. Conclusions In this pilot study, both CSF 25OHD level and CSF AChE activity were reduced in AD patients. However, the lack of correlations between 25OHD levels and CSF activities of AChE or BuChE might suggest different mechanisms of action, which could have implications for treatment trials. PMID:24312390

  19. Association between NME8 Locus Polymorphism and Cognitive Decline, Cerebrospinal Fluid and Neuroimaging Biomarkers in Alzheimer's Disease

    PubMed Central

    Liu, Ying; Yu, Jin-Tai; Wang, Hui-Fu; Hao, Xiao-Ke; Yang, Yu-Fen; Jiang, Teng; Zhu, Xi-Chen; Cao, Lei; Zhang, Dao-Qiang; Tan, Lan

    2014-01-01

    Recently, a large meta-analysis of five genome wide association studies (GWAS) identified a novel locus (rs2718058) adjacent to NME8 that played a preventive role in Alzheimer's disease (AD). However, this link between the single nucleotide polymorphism (SNP) rs2718058 and the pathology of AD have not been mentioned yet. Therefore, this study assessed the strength of association between the NME8 rs2718058 genotypes and AD-related measures including the cerebrospinal fluid (CSF) amyloid beta, tau, P-tau concentrations, neuroimaging biomarkers and cognitive performance, in a large cohort from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We used information of a total of 719 individuals, including 211 normal cognition (NC), 346 mild cognitive impairment (MCI) and 162 AD. Although we didn't observe a positive relationship between rs2718058 and AD, it was significantly associated with several AD related endophenotypes. Among the normal cognitively normal participants, the minor allele G carriers showed significantly associated with higher CDRSB score than A allele carriers (P?=?0.021). Occipital gyrus atrophy were significantly associated with NME8 genotype status (P?=?0.002), with A allele carriers has more atrophy than the minor allele G carriers in AD patients; lateral ventricle (both right and left) cerebral metabolic rate for glucose (CMRgl) were significantly associated with NME8 genotype (P<0.05), with GA genotype had higher metabolism than GG and AA genotypes in MCI group; the atrophic right hippocampus in 18 months is significantly different between the three group, with GG and AA genotypes had more hippocampus atrophy than GA genotypes in the whole group. Together, our results are consistent with the direction of previous research, suggesting that NME8 rs2718058 appears to play a role in lowering the brain neurodegeneration. PMID:25486118

  20. Plasma, cerebrospinal fluid, and brain distribution of /sup 14/C-melatonin in rat: a biochemical and autoradiographic study

    SciTech Connect

    Vitte, P.A.; Harthe, C.; Lestage, P.; Claustrat, B.; Bobillier, P.

    1988-01-01

    The distribution of 14C-Melatonin (14C-MT) after systemic injection was studied in the plasma, cerebrospinal fluid (CSF), and brain of rats. Chromatographic analysis (thin-layer chromatography and high-performance liquid chromatography) indicated that the radioactivity from biological samples taken at various times following the injection of label was mainly associated with 14C-MT. Computer analysis of plasma 14C-MT kinetics showed a three-compartment system with half-lives of 0.21 +/- 0.05, 5.97 +/- 1.11, and 47.52 +/- 8.86 min. The volume of distribution and the clearance were 1,736 +/- 349 ml.kg-1 and 25.1 +/- 1.7 ml.min-1.kg-1 respectively. The entry of 14C-MT into the CSF was rapid and reached a maximum at 5 min. The decay followed a two-compartment system with half-lives of 16.5 +/- 2.9 and 47.3 +/- 8.6 min. The CSF/plasma concentration ratio was 0.38 at the steady state (30 min). At 2 min the level of 14C-MT in the brain was 3.8 higher than in the CSF. Representative autoradiograms revealed an heterogeneous localization of 14C-MT in the grey matter. The highest regional values, as evaluated by the permeability area product technique, were found in cortex, thalamic nuclei, medial geniculate nucleus, anterior pretectal area, paraventricular nucleus of the hypothalamus, choroid plexuses, and bulb-pons. Thirty minutes later 14C-MT was still detected in most of the brain regions analyzed. These results point to a low but rapid penetration of circulating MT into the brain and the CSF. The heterogeneous distribution and the partial retention of 14C-MT in the brain are compatible with the hypothesis of a central action of this hormone mediated via binding sites.

  1. Follow-up investigations in cerebrospinal fluid of patients with dementia with Lewy bodies and Alzheimer's disease.

    PubMed

    Mollenhauer, B; Bibl, M; Trenkwalder, C; Stiens, G; Cepek, L; Steinacker, P; Ciesielczyk, B; Neubert, K; Wiltfang, J; Kretzschmar, H A; Poser, S; Otto, M

    2005-07-01

    Measuring proteins in cerebrospinal fluid (CSF) has gained wide acceptance for the differential diagnosis of dementia. Some groups have already extended these investigations in Alzheimer's disease (AD) by asking how stable these markers are in follow-up analysis, if they depend on the stage of disease and whether they can be used to monitor the progression and biological effects of treatment. We evaluated 21 patients with dementia with Lewy bodies (DLB) and 19 patients with AD, on two occasions, with regard to levels of tau protein, tau protein phosphorylated at threonine 181 (p-tau), Abeta42, Abeta40 and S-100B protein, using a set of commercially available assays. Tau protein levels were lower in DLB in first and second LP compared to AD and decreased during course of both groups. P-tau levels were increased in AD and DLB and decreased during follow-up. Abeta42 and Abeta40 remained relatively stable during follow-up but we found a slight increase of the median Abeta42 level in DLB, whereas in AD, Abeta42 tends to decrease during follow-up. S-100B protein increased during follow-up in both diseases. The protein dynamics in DLB and AD are relatively similar. S-100B protein may be a useful marker for follow-up in neurodegenerative diseases but has to be analysed in longer follow-up periods. Tau protein may be used to differentiate between DLB and AD. Follow-up CSF analyses are of limited value for the differentiation of AD and DLB. We conclude that more specific markers have to be established for the differentiation and follow-up of these diseases. PMID:15937638

  2. Neurocognitive decline in HIV patients is associated with ongoing T-cell activation in the cerebrospinal fluid

    PubMed Central

    Grauer, Oliver M; Reichelt, Doris; Grüneberg, Ute; Lohmann, Hubertus; Schneider-Hohendorf, Tilman; Schulte-Mecklenbeck, Andreas; Gross, Catharina C; Meuth, Sven G; Wiendl, Heinz; Husstedt, Ingo W

    2015-01-01

    Objective HIV-associated neurocognitive disorders (HAND) remain a challenge despite combination antiretroviral therapy (cART). Immune cell activation has been implicated to play a major role in the development of HAND. Methods In this study, we used multicolor flow cytometry on peripheral blood (PB) and cerebrospinal fluid (CSF) samples to determine the expression of HLA-DR and programmed death-1 (PD-1) on CD4+ and CD8+ T cells in patients with chronic HIV infection. Expression levels were correlated with HI virus load in PB and CSF, classification of HAND and severity of magnetic resonance imaging (MRI) signal abnormalities. Results In a cohort of 86 HIV patients we found that the grade of neurocognitive impairment and the severity of MRI signal abnormalities correlated with decreasing CD4/CD8-ratios and increased frequencies of HLA-DR expressing CD4+ and CD8+ T cells reaching the highest values in the CSF samples. Importantly, HLA-DR upregulation was still detectable in virologically suppressed HIV patients. Further, T-cell subpopulation analysis of 40 HIV patients showed a significant shift from naïve to effector memory (EM) T cells that was negatively correlated with the grade of neurocognitive impairment in the PB samples. Moreover, PD-1 was significantly increased on CD4+ memory T cells with highest levels on EM T cells in HIV patients with mild or severe neurocognitive alterations. Interpretation The CD4/CD8 ratio, the proportion of EM to naïve T cells and the immune activation profile of CD4+ and CD8+ T cells in PB and CSF might be useful parameters to monitor the efficacy of cART and to identify HIV patients at risk of further neurocognitive deterioration. PMID:26401512

  3. Bypassing hazard of housekeeping genes: their evaluation in rat granule neurons treated with cerebrospinal fluid of multiple sclerosis subjects

    PubMed Central

    Mathur, Deepali; Urena-Peralta, Juan R.; Lopez-Rodas, Gerardo; Casanova, Bonaventura; Coret-Ferrer, Francisco; Burgal-Marti, Maria

    2015-01-01

    Gene expression studies employing real-time PCR has become an intrinsic part of biomedical research. Appropriate normalization of target gene transcript(s) based on stably expressed housekeeping genes is crucial in individual experimental conditions to obtain accurate results. In multiple sclerosis (MS), several gene expression studies have been undertaken, however, the suitability of housekeeping genes to express stably in this disease is not yet explored. Recent research suggests that their expression level may vary under different experimental conditions. Hence it is indispensible to evaluate their expression stability to accurately normalize target gene transcripts. The present study aims to evaluate the expression stability of seven housekeeping genes in rat granule neurons treated with cerebrospinal fluid of MS patients. The selected reference genes were quantified by real time PCR and their expression stability was assessed using GeNorm and NormFinder algorithms. GeNorm identified transferrin receptor (Tfrc) and microglobulin beta-2 (B2m) the most stable genes followed by ribosomal protein L19 (Rpl19) whereas ?-actin (ActB) and glyceraldehyde-3-phosphate-dehydrogenase (Gapdh) the most fluctuated ones in these neurons. NormFinder identified Tfrc as the best invariable gene followed by B2m and Rpl19. ActB and Gapdh were the least stable genes as analyzed by NormFinder algorithm. Both methods reported Tfrc and B2m the most stably expressed genes and Gapdh the least stable one. Altogether our data demonstrate the significance of pre-validation of housekeeping genes for accurate normalization and indicates Tfrc and B2m as best endogenous controls in MS. ActB and Gapdh are not recommended in gene expression studies related to current one. PMID:26441545

  4. Use of the Hadad-Bassagasteguy flap for repair of recurrent cerebrospinal fluid leak after prior transsphenoidal surgery

    PubMed Central

    Brunworth, Joseph; Lin, Tina; Keschner, David B.; Garg, Rohit

    2013-01-01

    The Hadad-Bassagasteguy vascularized nasoseptal pedicled flap (HBF) is an effective technique for reconstruction of skull base defects with low incidence of postoperative cerebrospinal fluid (CSF) leak. Advanced planning is required as posterior septectomy during transsphenoidal surgery can preclude its use due to destruction of the vascular pedicle. We present four cases in which the HBF was successfully used to repair recurrent CSF leaks despite prior posterior septectomy and transsphenoidal surgery. A retrospective chart review was performed on all patients who developed recurrent CSF leak after transsphenoidal surgery over a 7-year period (2006–2013). Data were collected regarding demographics, clinical presentation, intraoperative findings, and surgical outcomes. Four patients who developed recurrent CSF drainage after transsphenoidal surgery were managed with HBF reconstruction during the study period. Two were men and two were women with a mean age of 37 years (range, 24–48 years). All had previously undergone resection of a pituitary macroadenoma via a transsphenoidal approach, with intraoperative CSF leaks repaired using multilayered free grafts. Recurrent CSF rhinorrhea arose 0.37–12 months (mean, 2.98 months) after the initial pituitary surgery. Active CSF drainage could be visualized intraoperatively with posterior septal perforations present. The HBF was successfully used in all cases, with no evidence of recurrent CSF leak after a mean follow-up of 2.35 years. The HBF may be salvaged for repair of recurrent CSF leaks even in the context of prior posterior septectomy and transsphenoidal surgery. However, longer follow-up is necessary to determine the long-term efficacy of this procedure in such revision cases. PMID:24498521

  5. Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

    PubMed Central

    Lahmann, Carolina; Kramer, Holger B.; Ashcroft, Frances M.

    2015-01-01

    Activating mutations in the Kir6.2 (KCNJ11) subunit of the ATP-sensitive potassium channel cause neonatal diabetes (ND). Patients with severe mutations also suffer from neurological complications. Glibenclamide blocks the open KATP channels and is the treatment of choice for ND. However, although glibenclamide successfully restores normoglycaemia, it has a far more limited effect on the neurological problems. To assess the extent to which glibenclamide crosses the blood-brain barrier (BBB) in vivo, we quantified glibenclamide concentrations in plasma, cerebrospinal fluid (CSF), and brain tissue of rats, control mice, and mice expressing a human neonatal diabetes mutation (Kir6.2-V59M) selectively in neurones (nV59M mice). As only small sample volumes can be obtained from rodents, we developed a highly sensitive method of analysis, using liquid chromatography tandem mass spectrometry acquisition with pseudo-selected reaction monitoring, achieving a quantification limit of 10ng/ml (20nM) glibenclamide in a 30?l sample. Glibenclamide was not detectable in the CSF or brain of rats after implantation with subcutaneous glibenclamide pellets, despite high plasma concentrations. Further, one hour after a suprapharmacological glibenclamide dose was administered directly into the lateral ventricle of the brain, the plasma concentration was twice that of the CSF. This suggests the drug is rapidly exported from the CSF. Elacridar, an inhibitor of P-glycoprotein and breast cancer resistance protein (major multidrug resistance transporters at the BBB), did not affect glibenclamide levels in CSF and brain tissue. We also identified a reduced sensitivity to volatile anaesthetics in nV59M mice and showed this was not reversed by systemic delivery of glibenclamide. Our results therefore suggest that little glibenclamide reaches the central nervous system when given systemically, that glibenclamide is rapidly removed across the BBB when given intracranioventricularly, and that any glibenclamide that does enter (and is below our detection limit) is insufficient to influence neuronal function as assessed by anaesthesia sensitivity. PMID:26225433

  6. Risk factors for first cerebrospinal fluid shunt infection: findings from a multi-center prospective cohort study

    PubMed Central

    Simon, Tamara D.; Butler, Jerry; Whitlock, Kathryn B.; Browd, Samuel R.; Holubkov, Richard; Kestle, John R.W.; Kulkarni, Abhaya V.; Langley, Marcie; Limbrick, David D.; Mayer-Hamblett, Nicole; Tamber, Mandeep; Wellons, John C.; Whitehead, William E.; Riva-Cambrin, Jay

    2014-01-01

    Objective To quantify the extent to which revision(s) of cerebrospinal fluid (CSF) shunt are associated with increased risk of CSF shunt infection, after adjusting for patient factors that may contribute to infection risk. Study design We used the HCRN registry to assemble a large prospective six center cohort of 1,036 children undergoing initial CSF shunt placement between April 2008 and January 2012. The primary outcome of interest was first CSF shunt infection. Data for initial CSF shunt placement and all subsequent CSF shunt revisions prior to first CSF shunt infection, where applicable, were obtained. The risk of first infection was estimated using a multivariable Cox proportional hazard model accounting for patient characteristics and CSF shunt revisions, and is reported using hazard ratios (HR) with 95% confidence intervals (CI). Results Of the 102 children who developed first infection within 12 months of placement, 33 (32%) followed one or more CSF shunt revisions. Baseline factors independently associated with risk of first infection included: gastrostomy tube (HR 2.0, 95% CI: 1.1, 3.3), age 6–12 months (HR 0.3, 95% CI: 0.1, 0.8), and prior neurosurgery (HR 0.4, 95% CI: 0.2, 0.9). After controlling for baseline factors, infection risk was most significantly associated with the need for revision (1 revision vs. none, HR 3.9, 95% CI: 2.2, 6.5; ?2 revisions, HR 13.0, 95% CI: 6.5, 24.9). Conclusions This study quantifies the elevated risk of infection associated with shunt revisions observed in clinical practice. To reduce risk of infection risk further work should optimize revision procedures. PMID:24661340

  7. A review article on the diagnosis and treatment of cerebrospinal fluid fistulas and dural tears occurring during spinal surgery

    PubMed Central

    Epstein, Nancy E.

    2013-01-01

    Background: In spinal surgery, cerebrospinal fluid (CSF) fistulas attributed to deliberate dural opening (e.g., for tumors, shunts, marsupialization of cysts) or inadvertent/traumatic dural tears (DTs) need to be readily recognized, and appropriately treated. Methods: During spinal surgery, the dura may be deliberately opened to resect intradural lesions/tumors, to perform shunts, or to open/marsupialize cysts. DTs, however, may inadvertently occur during primary, but are seen more frequently during revision spinal surgery often attributed to epidural scarring. Other etiologies of CSF fistulas/DTs include; epidural steroid injections, and resection of ossification of the posterior longitudinal ligament (OPLL) or ossification of the yellow ligament (OYL). Whatever the etiology of CSF fistulas or DTs, they must be diagnosed utilizing radioisotope cisternography (RIC), magnetic resonance imaging (MRI), computed axial tomography (CT) studies, and expeditiously repaired. Results: DTs should be repaired utilizing interrupted 7-0 Gore-Tex (W.L. Gore and Associates Inc., Elkton, MD, USA) sutures, as the suture itself is larger than the needle; the larger suture occludes the dural puncture site. Closure may also include muscle patch grafts, dural patches/substitutes (bovine pericardium), microfibrillar collagen (Duragen: Integra Life Sciences Holdings Corporation, Plainsboro, NJ), and fibrin glues or dural sealants (Tisseel: Baxter Healthcare Corporation, Deerfield, IL, USA). Only rarely are lumbar drains and wound-peritoneal and/or lumboperitoneal shunts warranted. Conclusion: DTs or CSF fistulas attributed to primary/secondary spinal surgery, trauma, epidural injections, OPLL, OYL, and other factors, require timely diagnosis (MRI/CT/Cisternography), and appropriate reconstruction. PMID:24163783

  8. Hemostasis and other benefits of fibrin sealants/glues in spine surgery beyond cerebrospinal fluid leak repairs

    PubMed Central

    Epstein, Nancy E.

    2014-01-01

    Background: Fibrin sealants (FS)/glues (FG) are primarily utilized in spinal surgery to either strengthen repairs of elective (e.g., intradural tumors/pathology) or traumatic cerebrospinal fluid (CSF) fistulas. Here, additional roles/benefits of FS/FG in spine surgery are explored; these include increased hemostasis, reduction of scar, reduction of the risk of infection if impregnated with antibiotics, and its application to restrict diffusion and limit some of the major complications attributed to the controversial “off-label” use of bone morphogeneitc protein (rhBMP-2/INFUSE). Methods: We reviewed multiple studies, focusing not just on the utility of FS/FG in the treatment of CSF fistulas, but on its other applications. Results: FS/FG have been primarily used to supplement elective/traumatic dural closure in spinal surgery. However, FS/FG also contribute to; hemostasis, reducing intraoperative/postoperative bleeding/transfusion requirements, length of stay (LOS)/costs, reduced postoperative scar/radiculitis, and infection when impregnated with antibiotics. Nevertheless, one should seriously question whether FS/FG should be applied to prevent diffusion and limit major complications attributed to the “off-label” use of BMP/INFUSE (e.g., limit/prevent heterotopic ossification, dysphagia/respiratory decompensation, and new neurological deficits). Conclusions: FS/FG successfully supplement watertight dural closure following elective (e.g., intradural tumor) or traumatic CSF fistulas occurring during spinal surgery. Additional benefits include: intraoperative hemostasis with reduced postoperative drainage, reduced transfusion requirements, reduced LOS, cost, scar, and prophylaxis against infection (e.g., impregnated with antibiotics). However, one should seriously question whether FS/FG should be used to contain the diffusion of BMP/INFUSE and limit its complications when utilized “off-label”. PMID:25289150

  9. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood

    PubMed Central

    Zetterberg, Henrik; Smith, Douglas H.; Blennow, Kaj

    2014-01-01

    Mild traumatic brain injury (TBI), which is defined as a head trauma resulting in a brief loss of consciousness and/or alteration of mental state, is usually benign, but occasionally causes persistent and sometimes progressive symptoms. Whether a threshold for the amount of brain injury and/or individual vulnerability might contribute to the development of these long-term consequences is unknown. Furthermore, reliable diagnostic methods that can establish whether a blow to the head has affected the brain (and in what way) are lacking. In this Review, we discuss potential biomarkers of injury to different structures and cell types in the CNS that can be detected in body fluids. We present arguments in support of the need for further development and validation of such biomarkers, and for their use in assessing patients with head trauma in whom the brain might have been affected. Specifically, we focus on the need for such biomarkers in the management of sports-related concussion, the most common cause of mild TBI in young individuals, to prevent long-term neurological sequelae due to concussive or subconcussive blows to the head. PMID:23399646

  10. Cerebrospinal Fluid Rhinorrhea and Seizure Caused by Temporo-Sphenoidal Encephalocele

    PubMed Central

    Baer, Ingrid; Geletneky, Karsten; Steiner, Hans-Herbert

    2015-01-01

    This case report describes the symptoms and clinical course of a 35-year-old female patient who was diagnosed with a temporo-sphenoidal encephalocele. It is characterized by herniation of cerebral tissue of the temporal lobe through a defect of the skull base localized in the middle fossa. At the time of first presentation the patient complained about recurrent nasal discharge of clear fluid which had begun some weeks earlier. She also reported that three months earlier she had for the first time suffered from a generalized seizure. In a first therapeutic attempt an endoscopic endonasal approach to the sphenoid sinus was performed. An attempt to randomly seal the suspicious area failed. After frontotemporal craniotomy, it was possible to localize the encephalocele and the underlying bone defect. The herniated brain tissue was resected and the dural defect was closed with fascia of the temporalis muscle. In summary, the combination of recurrent rhinorrhea and a first-time seizure should alert specialists of otolaryngology, neurology and neurosurgery of a temporo-sphenoidal encephalocele as a possible cause. Treatment is likely to require a neurosurgical approach. PMID:25932300

  11. A validated LC-MS/MS assay for quantification of 24(S)-hydroxycholesterol in plasma and cerebrospinal fluid[S

    PubMed Central

    Sidhu, Rohini; Jiang, Hui; Farhat, Nicole Y.; Carrillo-Carrasco, Nuria; Woolery, Myra; Ottinger, Elizabeth; Porter, Forbes D.; Schaffer, Jean E.; Ory, Daniel S.; Jiang, Xuntian

    2015-01-01

    24(S)-hydroxycholesterol [24(S)-HC] is a cholesterol metabolite that is formed almost exclusively in the brain. The concentrations of 24(S)-HC in cerebrospinal fluid (CSF) and/or plasma might be a sensitive marker of altered cholesterol metabolism in the CNS. A highly sensitive 2D-LC-MS/MS assay was developed for the quantification of 24(S)-HC in human plasma and CSF. In the development of an assay for 24(S)-HC in CSF, significant nonspecific binding of 24(S)-HC was observed and resolved with the addition of 2.5% 2-hydroxypropyl-?-cyclodextrin (HP-?-CD) into CSF samples. The sample preparation consists of liquid-liquid extraction with methyl-tert-butyl ether and derivatization with nicotinic acid. Good linearity was observed in a range from 1 to 200 ng/ml and from 0.025 to 5 ng/ml, for plasma and CSF, respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. Stability of 24(S)-HC was reported under a variety of storage conditions. This method has been successfully applied to support a National Institutes of Health-sponsored clinical trial of HP-?-CD in Niemann-Pick type C1 patients, in which 24(S)-HC is used as a pharmacodynamic biomarker. PMID:25866316

  12. Viral Meningitis

    MedlinePLUS

    ... Resources for Healthcare Professionals Related Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease Viral Meningitis Recommend on ... Arboviruses Lymphocytic Choriomeningitis Virus Related Links Vaccine Schedules Preteen & Teen Vaccines Meningococcal Disease File Formats Help: How ...

  13. Cryptococcal Meningitis

    MedlinePLUS

    ... a long period of time can lead to yeast infections (such as thrush , vaginitis, or severe candida ... cost and the risk of developing drug-resistant yeast infections. If you get meningitis, early diagnosis might ...

  14. Chronic Meningitis

    MedlinePLUS

    ... not infections can cause chronic meningitis. They include sarcoidosis and certain disorders that cause inflammation, such as ... For disorders that are not infections, such as sarcoidosis and Behçet syndrome: Corticosteroids or other drugs that ...

  15. Meningitis - meningococcal

    MedlinePLUS

    ... the most commonly used antibiotics for meningococcal meningitis. Penicillin in high doses is almost always effective, too. If the patient is allergic to penicillin, chloramphenicol may be used. Sometimes corticosteroids may be ...

  16. Meningitis - tuberculous

    MedlinePLUS

    ... include: Biopsy of the brain or meninges Blood culture Chest x-ray CSF examination for cell count, ... the head Gram stain, other special stains, and culture of CSF Polymerase chain reaction (PCR) of CSF ...

  17. Meningococcal meningitis and carriage in western Zaire: a hypoendemic zone related to climate?

    PubMed Central

    Cheesbrough, J. S.; Morse, A. P.; Green, S. D.

    1995-01-01

    An analysis of bacteria recovered from cerebrospinal fluid over a 16-year period at a rural hospital in western Zaire showed that Neisseria meningitidis accounted for only five (2.2%) isolates. A survey of naso-pharyngeal colonisation with N. meningitidis in 378 healthy children was undertaken to distinguish whether this low frequency was due to lack of carriage or, by inference, lack of the co-factors necessary to permit invasive disease. N. meningitidis was recovered from only three (0.78%) of the children. All isolates were non-typable strains of low pathogenicity. A review of studies examining the aetiology of bacterial meningitis and the geographical location of epidemics of meningococcal meningitis in and around Zaire reveals a 'hypoendemic zone', the limits of which correlate well with the area in which mean absolute humidity remains above 10 g m-3 of air throughout the year. Continuous high absolute humidity appears to reduce the transmission of meningococci. PMID:7867746

  18. First epidemic of aseptic meningitis due to echovirus type 13 among Spanish children.

    PubMed Central

    Trallero, G.; Casas, I.; Avellón, A.; Pérez, C.; Tenorio, A.; De La Loma, A.

    2003-01-01

    Echoviruses are the commonest cause of aseptic meningitis (AM). Echovirus type 13 (EV-13) was the second enterovirus serotype associated with different local outbreaks of AM in Spain between February and October 2000. It was the first time that an epidemic AM caused by this virus was recognized in Spain. The index case appeared in the Canary Islands (Canarias). The EV-13 virus was isolated from 135 patients, predominantly from cerebrospinal fluid (CSF). All isolates were from children under 13 years. The age specific peak incidence was in infants under 1 year. Most patients had fever, headache and other meningeal signs. This enterovirus serotype, not previously detected in Spain, caused severe illness with a high attack rate. PMID:12729193

  19. Clinical Aspects of Eosinophilic Meningitis and Meningoencephalitis caused by Angiostrongylus cantonensis, the Rat Lungworm

    PubMed Central

    Johnson, Stuart

    2013-01-01

    Angiostrongylus Eosinophilic Meningitis is caused by human infection with larvae of the rat lungworm, Angiostrongylus cantonensis. The clinical presentation includes a spectrum of disease, from meningitis through radiculitis, cranial nerve abnormalities, ataxia, encephalitis, coma, and rarely death. The condition is diagnosed by recognizing the triad of: the clinical syndrome, eosinophils in the cerebrospinal fluid or blood, and exposure history. A history of eating raw or poorly cooked snails is classic, but ingestion of other intermediate hosts or unwashed produce (such as lettuce) harboring hosts is not uncommon. Several serologic tests exist but none has yet been fully validated. There is good evidence that a 2 week course of high dose corticosteroids shortens the duration and severity of symptoms. There is somewhat weaker evidence that albendazole reduces symptoms. The combination of prednisolone and albendazole is being used more commonly for treatment. Some suggestions for future research are given. PMID:23901382

  20. Chronic granulomatous meningitis with multiple cranial nerve lesions hydrocephalus, stroke, sinus thrombosis, and epilepsy.

    PubMed

    Finsterer, J; Kladosek, A; Nagelmeier, I E; Becherer, A; Matula, C; Stradal, K H; Wolf, K; Czech, T; Stanek, G

    2000-11-01

    Most frequently, chronic granulomatous meningitis (CGM) is caused by infectious agents. However, in some cases the cause of CGM remains undetermined. It is unclear whether antimicrobial agents, including antituberculous drugs, are helpful in such cases. We describe a 61-year-old man who had multiple cranial nerve lesions, epilepsy, sinus thrombosis, stroke, and hydrocephalus attributable to CGM. Repeated extensive search for a causative agent in the cerebrospinal fluid (CSF) and the meninges remained negative. Only a single culture of the sputum revealed growth of Mycobacterium tuberculosis, which prompted antituberculous therapy with isoniazid, rifampicin, and ethambutol. After 6 months of therapy, neurologic abnormalities were slightly improved. We conclude that antimicrobial/ antituberculous agents have only a minor short-term effect in long-lasting CGM of undetermined cause. PMID:11095565

  1. Study of the Frequency of Herpesvirus Infections Among Patients Suspected Aseptic Meningitis in the West of Iran

    PubMed Central

    Akya, Alisha; Ahmadi, Kamal; Zehtabian, Shahram; Salimi, Afsaneh; Elahi, Azam; Madani, Sayed Hamid

    2015-01-01

    Background: Aseptic meningitis is the most common type of meningitis and is characterized by meningeal inflammation that is not linked to identifiable bacterial pathogens in cerebrospinal fluid (CSF). Objectives: This study aimed to evaluate the frequency of aseptic meningitis caused by herpesviruses, namely herpes simplex types I and II (HSV-1, HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella-zoster virus (VZV). Patients and Methods: A total of 196 CSF samples were collected from patients with suspected meningitis. All samples were smear- and culture-negative for bacterial pathogens. The biochemical and cytological findings of CSF samples were also recorded. DNA was extracted from samples and PCR with specific primers was carried out to detect viruses. Results: The 196 samples derived from 100 (52%) men and 96 (48%) women ranging in age from one day to 86 years with an average age of 32.3 ± 25.3 years. Of them, 8 (4.08%) samples yielded positive results, including 5 (2.55%) cases of VZV infection and 3 (1.53%) cases of HSV-1 infection. No cases of HSV-2, CMV or EBV infection were detected. CSF protein and glucose levels among positive cases were all in the normal range. Conclusions: The results indicate a considerable rate of herpesvirus infection in patients with aseptic meningitis, and that VZV is the most common herpesvirus to cause infection followed by HSV-1. Our results also showed that a moderate increase in the WBC count and predominance of lymphocytes can be valuable clues in diagnosing viral meningitis. Given the different approaches of drug therapy in bacterial and viral meningitis, use of molecular methods is necessary in hospitals to rapidly discriminate between them. PMID:26568804

  2. Meningitis and Encephalitis

    MedlinePLUS

    ... Awards Enhancing Diversity Find People About NINDS NINDS Meningitis and Encephalitis Information Page Synonym(s): Meningitis, Encephalitis Condensed ... en Español Additional resources from MedlinePlus What are Meningitis and Encephalitis? Meningitis and encephalitis are inflammatory diseases ...

  3. Cerebrospinal Fluid (CSF) CD8+ T-Cells That Express Interferon-Gamma Contribute to HIV Associated Neurocognitive Disorders (HAND)

    PubMed Central

    Schrier, Rachel D.; Hong, Suzi; Crescini, Melanie; Ellis, Ronald; Pérez-Santiago, Josué; Spina, Celsa; Letendre, Scott

    2015-01-01

    Background HIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis. Methods To investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFN?, IL-2, TNF?) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART. Results Data were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNF?, IL-2, IFN? and CD8+T-cells: IL-2 and IFN?. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFN? expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFN? and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/?l and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFN? expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF. Conclusions Presence of IFN? expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND. PMID:25719800

  4. Cerebrospinal Fluid Dendritic Cells Infiltrate the Brain Parenchyma and Target the Cervical Lymph Nodes under Neuroinflammatory Conditions

    PubMed Central

    Hatterer, Eric; Touret, Monique; Belin, Marie-Françoise; Honnorat, Jérôme; Nataf, Serge

    2008-01-01

    Background In many neuroinflammatory diseases, dendritic cells (DCs) accumulate in several compartments of the central nervous system (CNS), including the cerebrospinal fluid (CSF). Myeloid DCs invading the inflamed CNS are thus thought to play a major role in the initiation and perpetuation of CNS-targeted autoimmune responses. We previously reported that, in normal rats, DCs injected intra-CSF migrated outside the CNS and reached the B-cell zone of cervical lymph nodes. However, there is yet no information on the migratory behavior of CSF-circulating DCs under neuroinflammatory conditions. Methodology/Principal Findings To address this issue, we performed in vivo transfer experiments in rats suffering from experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. EAE or control rats were injected intra-CSF with bone marrow-derived myeloid DCs labeled with the fluorescent marker carboxyfluorescein diacetate succinimidyl ester (CFSE). In parallel experiments, fluorescent microspheres were injected intra-CSF to EAE rats in order to track endogenous antigen-presenting cells (APCs). Animals were then sacrificed on day 1 or 8 post-injection and their brain and peripheral lymph nodes were assessed for the presence of microspheres+ APCs or CFSE+ DCs by immunohistology and/or FACS analysis. Data showed that in EAE rats, DCs injected intra-CSF substantially infiltrated several compartments of the inflamed CNS, including the periventricular demyelinating lesions. We also found that in EAE rats, as compared to controls, a larger number of intra-CSF injected DCs reached the cervical lymph nodes. This migratory behavior was accompanied by an accentuation of EAE clinical signs and an increased systemic antibody response against myelin oligodendrocyte glycoprotein, a major immunogenic myelin antigen. Conclusions/Significance Altogether, these results indicate that CSF-circulating DCs are able to both survey the inflamed brain and to reach the cervical lymph nodes. In EAE and maybe multiple sclerosis, CSF-circulating DCs may thus support the immune responses that develop within and outside the inflamed CNS. PMID:18830405

  5. Neurotransmitter levels in cerebrospinal fluid in relation to severity of symptoms and response to medical therapy in Parkinson's disease.

    PubMed

    Ondarza, R; Velasco, F; Velasco, M; Aceves, J; Flores, G

    1994-01-01

    Determinations of biopterin (BP), homovanilic acid (HVA), glutamic acid (GTA), and glutamine (GT) levels in cerebrospinal fluid (CSF) obtained through a lumbar tap were performed in 20 parkinsonian patients in different stages of evolution and without medication. In patients with motor symptoms not related to Parkinson's disease (dystonia, dyskinesia and essential tremor) (n = 4). In 7 other neurological patients subjected to spinal tap for diagnostic procedures neurotransmitters were also determined and taken as control groups. In 14 of the patients with Parkinson's disease, the symptoms were evaluated using conventional scales (UPDS, NYPDS, NWPDS, Schwab and England, and Hoehn and Yahr scale). The amplitude and the frequency of tremor were quantitatively evaluated through a single plane accelerometer Grass SP-1, akinesia was measured through reaction time to auditory stimuli, and rigidity through the speed of lineal movement. Evaluations were performed with the patient not on any medication for 1 week and repeated 1 h after the intake of 250 mg of 200/50 L-dopa/carbidopa preparation (Sinemet) and on a different day after the intake of biperiden (Akineton) 6 mg/day. Differences in neurotransmitter or metabolites levels between Parkinson's disease and control groups were determined through an independent Student's t test. Correlation between severity of symptoms in the scales and for each individual symptom measured through the quantitative tests and the levels of neurotransmitters in CSF were evaluated through the Pearson correlation analysis test. Modifications in the motor performance after administration of Sinemet and Akineton, and the levels of neurotransmitters were indirectly determined. RESULTS. (1) There were significant differences between the levels of BP and GT in patients with Parkinson's disease and control groups, (2) lower GTA levels correlated with more severe rigidity and akinesia, and with the best response to the administration of L-dopa and may be an important marker for prognosis, and (3) lower levels of GT correlated with least akinesia, but not with tremor, which may indicate that the akinesia depends on other biochemical abnormalities besides dopamine depletion. PMID:7631094

  6. Genetic Loci Associated with Alzheimer’s Disease and Cerebrospinal Fluid Biomarkers in a Finnish Case-Control Cohort

    PubMed Central

    Natunen, Teemu; Hall, Anette; Paajanen, Teemu; Herukka, Sanna-Kaisa; Laitinen, Marjo; Remes, Anne M.; Koivisto, Anne M.; Mattila, Kari M.; Lehtimäki, Terho; Verhey, Frans R. J.; Visser, Pieter Jelle; Soininen, Hilkka; Hiltunen, Mikko

    2013-01-01

    Objectives To understand the relation between risk genes for Alzheimer’s disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers A?1–42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Methods We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland. Results APOE-?4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased A?1–42 (corrected p<0.05). At an uncorrected p<0.05, PPP3R1 rs1868402 and MAPT rs2435211 were related with increased t-tau; while SORL1 rs73595277 and MAPT rs16940758, with increased p-tau. Only TOMM40 rs2075650 showed association with clinical AD after adjusting for APOE-?4 (p?=?0.007), but not after multiple test correction (p>0.05). Conclusions We provide evidence that APOE-?4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF A?1–42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-?4, CLU and MS4A4A influence both AD risk and CSF A?1–42. PMID:23573206

  7. Cerebrospinal Fluid Melanin-Concentrating Hormone (MCH) and Hypocretin-1 (HCRT-1, Orexin-A) in Alzheimer’s Disease

    PubMed Central

    Schmidt, Frank M.; Kratzsch, Juergen; Gertz, Hermann-Josef; Tittmann, Mandy; Jahn, Ina; Pietsch, Uta-Carolin; Kaisers, Udo X.; Thiery, Joachim; Hegerl, Ulrich; Schönknecht, Peter

    2013-01-01

    Ancillary to decline in cognitive abilities, patients with Alzheimer’s disease (AD) frequently suffer from behavioural and psychological symptoms of dementia (BPSD). Hypothalamic polypeptides such as melanin-concentrating hormone (MCH) and hypocretin-1 (HCRT-1, orexin-A) are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF) levels were measured in 33 patients with AD and 33 healthy subjects (HS) using a fluorescence immunoassay (FIA). A significant main effect of diagnosis (F(1,62)?=?8.490, p<0.01) on MCH levels was found between AD (93.76±13.47 pg/mL) and HS (84.65±11.40 pg/mL). MCH correlated with T-tau (r?=?0.47; p<0.01) and P-tau (r?=?0.404; p<0.05) in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r?=??0.362, p<0.05) and was increased in more severely affected patients (MMSE?20) compared to HS (p<0.001) and BPSD-positive patients compared to HS (p<0.05). In CSF-HCRT-1, a significant main effect of sex (F(1,31)?=?4.400, p<0.05) with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL) was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD. PMID:23667582

  8. Immunohistochemical analysis of transporters related to clearance of amyloid-? peptides through blood-cerebrospinal fluid barrier in human brain.

    PubMed

    Matsumoto, Koichi; Chiba, Yoichi; Fujihara, Ryuji; Kubo, Hiroyuki; Sakamoto, Haruhiko; Ueno, Masaki

    2015-12-01

    A large number of previous reports have focused on the transport of amyloid-? peptides through cerebral endothelial cells via the blood-brain barrier, while fewer reports have mentioned the transport through the choroid plexus epithelium via the blood-cerebrospinal fluid barrier. Concrete roles of these two pathways remain to be clarified. In this study, we immunohistochemically examined the expression of transporters/receptors that are supposed to be related to the clearance of amyloid-? peptides in the choroid plexus epithelium, the ventricular ependymal cells and the brain microvessels, using seven autopsied human brains. In the choroid plexus epithelium, immunoreactivity for low-density lipoprotein receptor (LDLR), LDLR-related protein 1 (LRP1), LRP2, formylpeptide receptor-like 1 (FPRL1), ATP-binding cassette (ABC) transporter-A1 (ABCA1), ABCC1 and ABCG4 was seen in 7 of 7 brains, while that for ABCB1, ABCG2, RAGE and CD36 was seen in 0-2 brains. In the ventricular ependymal cells, immunoreactivity for CD36, LDLR, LRP1, LRP2, FPRL1, ABCA1, ABCC1 and ABCG4 was seen in 6-7 brains, while that for ABCB1, ABCG2 and RAGE was seen in 0-1 brain. Immunoreactivity for insulin-degrading enzyme (IDE) was seen in three and four brains in the choroid plexus epithelium and the ventricular ependymal cells, respectively. In addition, immunoreactivity for LDLR, ABCB1 and ABCG2 was seen in over 40 % of the microvessels (all seven brains), and that for FPRL1, ABCA1, ABCC1 and RAGE was seen in over 5 % of the microvessels (4-6 brains), while that for CD36, IDE, LRP1, LRP2 and ABCG4 was seen in less than 5 % of the microvessels (0-2 brains). These findings may suggest that these multiple transporters/receptors and IDE expressed on the choroid plexus epithelium, ventricular ependymal cells and brain microvessels complementarily or cooperatively contribute to the clearance of amyloid-? peptides from the brain. PMID:26449856

  9. Cerebrospinal Fluid A?40 Improves the Interpretation of A?42 Concentration for Diagnosing Alzheimer’s Disease

    PubMed Central

    Dorey, Aline; Perret-Liaudet, Armand; Tholance, Yannick; Fourier, Anthony; Quadrio, Isabelle

    2015-01-01

    The combination of decreased amyloid ?42 (A?42) and increased total tau proteins (T-Tau) and phosphorylated tau (P-Tau) in cerebrospinal fluid (CSF) has recently been considered as a biological diagnostic criterion of Alzheimer’s disease (AD). Previous studies showed significant heterogeneity in CSF A?42 levels to discriminate AD from non-AD patients. It was also suggested that the CSF amyloid peptide ?42/?40 ratio has better diagnostic performance than A?42 alone. The objective of the present study was to investigate the potential added value of determining CSF amyloid ?40 peptide (A?40) for biological diagnosis of AD when CSF A?42 levels failed. CSF AD biomarkers were run in 2,171 samples from 1,499 AD and 672 non-AD patients. The following pathologic thresholds were used to define an AD-positive CSF biomarker profile: T-Tau???400?ng/L, P-Tau181???60?ng/L, and A?42???700?ng/L. CSF A?40 was assayed in AD patients with CSF A?42 levels above 700?ng/L and non-AD patients with CSF A?42 levels below 700?ng/L. CSF A?40 levels were higher in AD than non-AD patients. The receiver operator characteristic curves of CSF A?40 and the A?42/A?40 ratio defined AD cut-off values at 12,644?ng/L and 0.06, respectively. In AD patients with non-pathological CSF A?42, CSF A?40 concentration was able to correct 76.2% of cases when expressed as CSF A?42/A?40 ratio and 94.7% of cases when used alone. Using CSF A?42 and then CSF A?40, the percentage of misinterpreted AD patients fell to 1.0%. CSF A?40 concentration improved interpretation of A?42 level for the diagnosis of AD. CSF A?40 alone showed better diagnostic performance than the amyloid peptide A?42/A?40 ratio. The added value of determining CSF A?40 in AD diagnosis now needs confirming in a cohort of definite AD patients and to be completed with novel amyloid cascade biomarkers. PMID:26640457

  10. Neisseria sicca meningitis following intracranial hemorrhage and ventriculostomy tube placement.

    PubMed

    Carter, J Elliot; Mizell, Kelly N; Evans, Tara N

    2007-12-01

    A normal component of the flora of the oropharynx, Neisseria sicca was first isolated in 1906 and has since been reported as a rare cause of various human infections including endocarditis, pneumonia, sinusitis, sepsis, and urethritis. We report the case of a 44-year-old African-American female with a history of hypertension who presented with complaints of right frontal headache, nausea, photophobia, and vomiting. A computed tomography scan of the patient's brain showed a large subarachnoid hemorrhage, and an arteriogram confirmed a large posterior communicating artery aneurysm. A ventriculostomy tube was placed, and the patient subsequently developed an elevated temperature and elevated white blood cell count. Cerebrospinal fluid studies showed elevated protein and glucose levels and cultures positive for N. sicca. This is only the seventh reported case of culture-proven meningitis related to N. sicca, and the first reported case associated with intracranial hemorrhage and ventriculostomy tube placement. PMID:17904282

  11. Immunocytochemical Method for Early Laboratory Diagnosis of Tuberculous Meningitis

    PubMed Central

    Sumi, M. G.; Mathai, A.; Reuben, S.; Sarada, C.; Radhakrishnan, V. V.

    2002-01-01

    A simple immunocytochemical method was standardized for the direct demonstration of mycobacterial antigen in cerebrospinal fluid (CSF) specimens of patients with tuberculous meningitis (TBM). CSF-cytospin smears were prepared from 22 patients with a clinical diagnosis of TBM and also from an equal number of patients with nontuberculous neurological diseases (disease control). Immunocytological demonstration of mycobacterial antigens in the cytoplasm of monocytoid cells was attempted, by using rabbit immunoglobulin G to Mycobacterium tuberculosis as the primary antibody. Of the 22 CSF-cytospin smears from TBM patients, 16 showed positive immunostaining, while all of the CSF-cytospin smears from the disease control showed negative immunostaining for mycobacterial antigen. The technical aspects of this immunocytological method for the demonstration of mycobacterial antigens are simple, rapid, and reproducible, as well as specific, and therefore can be applied for the early diagnosis of TBM, particularly in patients in whom bacteriological methods did not demonstrate the presence of M. tuberculosis in the CSF. PMID:11874875

  12. A pituitary abscess masquerading as recurrent hypernatremia and aseptic meningitis

    PubMed Central

    Gonzales, Michael; Marik, Paul Ellis; Khardori, Romesh K; O'Brian, John T

    2012-01-01

    Pituitary abscess is a rare condition. In the setting of multiple surgical interventions, the risk of its development increases. A 49-year-old man presented with episodes of altered mental status. He had two surgeries for a recurrent suprasellar arachnoid cyst. The second surgery was complicated by a persistent cerebrospinal fluid (CSF) leak that required two repairs following which he developed panhypopituitarism and central diabetes insipidus. Twelve months after his last surgery he was diagnosed with aseptic meningitis. This was followed by recurrent hospitalisations for severe hypernatremia blamed on poor medication compliance. He was subsequently hospitalised for the evaluation of a febrile illness. Brain MRI showed ventriculitis and enhancement of the sella. Exploratory surgery revealed a purulent collection in the sella and a mucosal graft which had been used to repair the CSF leak. After drainage of pus and replacement of the graft he recovered completely but requiring life-long hormonal replacement. PMID:22751424

  13. Leptomeningeal carcinomatosis from oesophageal cancer, presenting as meningitis.

    PubMed

    Ahmed, Mashrafi; Begum, Tahmina; Omer, Abdel Rahman; Khan, Ishtiaque Amin

    2016-01-01

    A 47-year-old woman presented with headache, neck pain, dizziness, nausea and vomiting for 4-5?days. She also had a history of weight loss and difficulty in swallowing. On physical examination, she had nuchal rigidity with a positive Kernig's sign. Cerebrospinal fluid analysis revealed mild pleocytosis but some atypical cells were also noted. Cytopathological analysis of the atypical cells showed high nuclear/cytoplasmic ratios and eccentric nuclei with prominent nucleoli, consistent with malignancy. A CT scan of the head and neck showed multiple lytic lesions involving the left calvarium, and diffuse thickening and enhancement of meninges over the left cerebral area. Extensive osteolytic lesions were also noted on the vertebral bodies, pedicles and lamina, at multiple levels of the cervical spine. An endoscopy revealed a mass at the gastro-oesophageal junction, and biopsy confirmed moderately differentiated adenocarcinoma of the oesophagus. The patient was started on chemotherapy along with radiation therapy. PMID:26740266

  14. Current concepts of bacterial infections of the central nervous system. Bacterial meningitis and bacterial brain abscess.

    PubMed

    Garvey, G

    1983-11-01

    Investigative work continues to provide guidance toward more rational management of bacterial meningitis and bacterial brain abscess. An increased understanding of the host's response in cases of bacterial meningitis has established that diffusibility of an antibiotic into the cerebrospinal fluid (CSF) is necessary, but is not sufficient for microbial cure. The antibiotic must also have a bactericidal effect on the pathogen. Meningitis after neurosurgery may be caused by Gram-negative aerobic bacilli. In some of these cases the newer cephalosporin antibiotics may be a useful advance. Meningitis complicating ventricular CSF shunts presents a paradigm for the problem of eradicating foreign body-related infections. Studies of the interaction of the host, the organism, and the shunt material offer some explanation for the limited efficacy of antibiotics observed in this setting. There have been advances in microbial definition of bacterial brain abscess. The identification of Bacteroides fragilis as a pathogen in certain brain abscesses has established a role for a newly available antibiotic, metronidazole. The study of the pathological distinction between cerebritis and frank abscess is clarifying two clinical characteristics of brain abscess: the limited success of antibiotic treatment and the increase in intracranial pressure. Computerized tomography has offered a valuable clinical "look" at brain abscesses; however, there are still problems in correlating the scan images with the evolving pathological process. PMID:6352873

  15. Varicella Zoster Aseptic Meningitis: Report of an Atypical Case and Literature Review

    PubMed Central

    Ibrahim, Walid; Elzouki, Abdel-Naser; Husain, Ahmed; Osman, Lubna

    2015-01-01

    Patient: Female, 15 Final Diagnosis: Varicella Zoster aseptic meningitis Symptoms: — Medication: — Clinical Procedure: Lumber punctur Specialty: Infectious Diseases Objective: Unusual clinical course Background: Neurologic complications can occur with varicella zoster virus (VZV) infection, usually after vesicular exanthem. A review of the literature revealed 3 cases of viral meningitis associated with 6th nerve palsy but without significantly increased intracranial pressure. Case Report: We report a case of a previously healthy 15-year-old girl with aseptic meningitis as a result of reactivated-VZV infection with symptoms of increased intracranial pressure and reversible 6th cranial nerve palsy but without exanthema. Diagnosis was made by detection of VZV-DNA in cerebrospinal fluid using polymerase chain reaction and documented high intracranial pressure. Full recovery was achieved after a course of acyclovir and acetazolamide. Conclusions: This case demonstrates that VZV may be considered in cases of aseptic meningitis in immunocompetent individuals, even without exanthema, and it may increase the intracranial pressure, leading to symptoms, and causing reversible neurological deficit. PMID:26342350

  16. Hemophilus influenzae meningitis in the rat: behavioral, electrophysiological, and biochemical consequences.

    PubMed

    Konkol, R J; Chapman, L; Breese, G R; Collier, A M; Kilts, C; Finley, C; Vogel, R R; Mailman, R B; Bendeich, E G

    1987-04-01

    Hemophilus influenzae is the most common cause of bacterial meningitis in children, and a high percentage of survivors are at risk for long-term sequelae. To explore the mechanisms responsible for these sequelae, a neonatal rat model was used to define the behavioral, electrophysiological, and biochemical changes following meningitis. Three days after inoculation of 6-day-old rats with a minimum of 1 X 10(7) colony-forming units of a virulent Hemophilus influenzae, type b, cerebrospinal fluid and blood were cultured to confirm the presence of meningitis and bacteremia, respectively. At this time, forebrain norepinephrine and dopamine levels were significantly elevated in meningitic rats when standardized on a wet-weight basis. No changes in brain serotonin or heart norepinephrine levels could be found in the 9-day-old rats. No residual changes were found in steady-state concentrations of norepinephrine or dopamine in surviving adult rats. However, survivors that had had meningitis as neonates showed significant impairment in active and passive avoidance learning tasks and demonstrated a significantly higher level of activity during a habituation period in circular photocell activity cages. No change in the flinch-jump threshold was detected. Brainstem auditory evoked potentials showed delays of various waves in 3 of 10 Hemophilus influenzae type b-treated adult rats tested. These rats also exhibited markedly augmented locomotory responses to d-amphetamine (1 mg/kg), suggesting a long-lasting perturbation of central monoamine neuronal transmission. PMID:3579220

  17. Alterations of the cerebrospinal fluid proteins and subcommissural organ secretion in the arterial hypertension and ventricular dilatation. A study in SHR rats.

    PubMed

    Martínez-Peña y Valenzuela, I; Carmona-Calero, E M; Pérez-González, H; Ormazabal-Ramos, C; Fernández-Rodríguez, P; González-Marrero, I; Castañeyra-Perdomo, A; Ferres-Torres, R

    2006-02-01

    The aim of this work was to analyze the proteins in the cerebrospinal fluid (CSF) of spontaneously hypertensive rats, to study their possible role in the relationship between hydrocephalus, arterial hypertension and alterations in the subcommissural organ. Brains from control Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) sacrificed with chloral hydrate were used. Antiserums against some cerebrospinal fluid protein bands and Reissner's fiber (RF) were used for immunohistochemical study of the SCO. Ventricular dilation was observed in the lateral and third ventricle of the SHR. Third ventricle ependyma showed immunoreactive material (IRM) for antibody against 141 kDa protein band anti-B1 and 117 protein band anti-B2 and the SCO of the SHR showed a decrease of the IRM when compared with WKY rats. An alteration in the expression of anti-RF was found to compare the SCO of the WKY and SHR groups. Our results demonstrate that hydrocephalus and hypertension are interconnected in this kind of rat which produce alterations in SCO secretions and some proteins of the CSF. PMID:16329042

  18. Proteoform analysis of lipocalin-type prostaglandin D-synthase from